Journal Description
Pharmaceutics
Pharmaceutics
is a peer-reviewed, open access journal on the science and technology of pharmaceutics and biopharmaceutics, and is published monthly online by MDPI. The Spanish Society of Pharmaceutics and Pharmaceutical Technology (SEFIG), Pharmaceutical Solid State Research Cluster (PSSRC), Academy of Pharmaceutical Sciences (APS) and Korean Society of Pharmaceutical Sciences and Technology (KSPST) are affiliated with Pharmaceutics and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q1 (Pharmaceutical Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.2 days after submission; acceptance to publication is undertaken in 3.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journal: Future Pharmacology
Impact Factor:
5.4 (2022);
5-Year Impact Factor:
6.0 (2022)
Latest Articles
Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip
Pharmaceutics 2024, 16(5), 574; https://doi.org/10.3390/pharmaceutics16050574 - 23 Apr 2024
Abstract
The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a
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The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient ( and the apparent permeability (). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.
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(This article belongs to the Collection Feature Papers in Pharmaceutical Technology)
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Exploring the Wound Healing Potential of a Cuscuta chinensis Extract-Loaded Nanoemulsion-Based Gel
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Nichcha Nitthikan, Weeraya Preedalikit, Kanittapon Supadej, Siripat Chaichit, Pimporn Leelapornpisid and Kanokwan Kiattisin
Pharmaceutics 2024, 16(5), 573; https://doi.org/10.3390/pharmaceutics16050573 - 23 Apr 2024
Abstract
Cuscuta chinensis (C. chinensis) presents many pharmacological activities, including antidiabetic effects, and antioxidant, anti-inflammatory, and antitumor properties. However, the wound care properties of this plant have not yet been reported. Therefore, this research aimed to evaluate the antioxidant, anti-inflammatory, and antibacterial
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Cuscuta chinensis (C. chinensis) presents many pharmacological activities, including antidiabetic effects, and antioxidant, anti-inflammatory, and antitumor properties. However, the wound care properties of this plant have not yet been reported. Therefore, this research aimed to evaluate the antioxidant, anti-inflammatory, and antibacterial activities of ethanol and ethyl acetate C. chinensis extracts. The phytochemical markers in the extracts were analyzed using high-performance liquid chromatography (HPLC). Then, the selected C. chinensis extract was developed into a nanoemulsion-based gel for wound care testing in rats. The results showed that both of the C. chinensis extracts exhibited antioxidant activity when tested using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and lipid peroxidation inhibition assays. They reduced the expression of IL-1β, IL-6, and TNF-α in RAW264.7 cells induced with lipopolysaccharide (LPS). The ethyl acetate extract also had antibacterial properties. Kaempferol was found in both extracts, whereas hyperoside was found only in the ethanol extract. These compounds were found to be related to the biological activities of the extracts, confirmed via molecular docking. The C. chinensis extract-loaded nanoemulsions had a small particle size, a narrow polydispersity index (PDI), and good stability. Furthermore, the C. chinensis extract-loaded nanoemulsion-based gel had a positive effect on wound healing, presenting a better percentage wound contraction Fucidin cream. In conclusion, this formulation has the potential for use as an alternative wound treatment and warrants further study in clinical trials.
Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
Open AccessArticle
Physicochemical Stability of Hospital Parenteral Nutrition Solutions: Effect of Changes in Composition and Storage Protocol
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Luis Otero-Millán, Brais Bea-Mascato, Jose Luis Legido Soto, Noemi Martínez-López-De-Castro and Natividad Lago-Rivero
Pharmaceutics 2024, 16(5), 572; https://doi.org/10.3390/pharmaceutics16050572 - 23 Apr 2024
Abstract
(1) Background: Parenteral nutrition (PN) is a technique used for the administration of nutrients to patients for whom traditional routes cannot be used. It is performed using solutions with extremely complex compositions, which can give rise to a large number of interactions. These
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(1) Background: Parenteral nutrition (PN) is a technique used for the administration of nutrients to patients for whom traditional routes cannot be used. It is performed using solutions with extremely complex compositions, which can give rise to a large number of interactions. These interactions can impact their stability and put the patient’s life at risk. The aim of this study is to determine how changes in composition and storage protocol affect the stability of NP solutions. (2) Methods: Twenty-three samples were prepared according to routine clinical practice, with modifications to the concentration of some components. The samples were stored at room temperature (RT) and refrigerated (4 °C). Measurements of the droplet diameter, pH, density and viscosity were performed for both storage protocols on days 1, 3, 10 and 14. (3) Results: The samples with the lowest concentration of lipids (PN13-17) and proteins (PN18-22) showed a larger droplet diameter than the rest of the samples throughout the experiments. The USP limits were exceeded for some of the measurements of these sample groups. The pH density and viscosity remained relatively constant under the conditions studied. (4) Conclusions: The PN samples were considered stable and safe for administration under real-world conditions, but the samples with the lowest concentrations of lipids and proteins showed a tendency towards emulsion instability.
Full article
(This article belongs to the Special Issue Stability of Medicines and Novel Approaches for Predicting Drug Stability)
Open AccessArticle
Evaluation of the Transport and Binding of Dopamine-Loaded PLGA Nanoparticles for the Treatment of Parkinson’s Disease Using In Vitro Model Systems
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Karin Danz, Jana Fleddermann, Marcus Koch, Elena Fecioru, Lorenz Maahs, Nicole Kinsinger, Johannes Krämer, Annette Kraegeloh and Sylvia Wagner
Pharmaceutics 2024, 16(5), 571; https://doi.org/10.3390/pharmaceutics16050571 - 23 Apr 2024
Abstract
The treatment of Parkinson’s disease has been moving into the focus of pharmaceutical development. Yet, the necessity for reliable model systems in the development phase has made research challenging and in vivo models necessary. We have established reliable, reproducible in vitro model systems
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The treatment of Parkinson’s disease has been moving into the focus of pharmaceutical development. Yet, the necessity for reliable model systems in the development phase has made research challenging and in vivo models necessary. We have established reliable, reproducible in vitro model systems to evaluate the binding and transport of dopamine-loaded PLGA nanoparticles for the treatment of Parkinson’s disease and put the results in context with comparable in vivo results. The in vitro models have provided similar results concerning the usability of the investigated nanoparticles as the previously used in vivo models and thus provide a good alternative in line with the 3R principles in pharmaceutical research.
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(This article belongs to the Section Nanomedicine and Nanotechnology)
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Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer
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Rulei Yang, Yiran Liu, Ning Yang, Tian Zhang, Jiazhen Hou, Zongyan He, Yutong Wang, Xujie Sun, Jingshan Shen, Hualiang Jiang, Yuanchao Xie and Tianqun Lang
Pharmaceutics 2024, 16(4), 570; https://doi.org/10.3390/pharmaceutics16040570 - 22 Apr 2024
Abstract
Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid
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Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.
Full article
(This article belongs to the Special Issue Lipid-Based Nanoparticles for Drug Delivery in Cancer)
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Open AccessReview
Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?
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Mohamed Salla, Nadine Karaki, Belal El Kaderi, Abeer J. Ayoub, Samar Younes, Maya N. Abou Chahla, Shairaz Baksh and Sami El Khatib
Pharmaceutics 2024, 16(4), 569; https://doi.org/10.3390/pharmaceutics16040569 - 22 Apr 2024
Abstract
Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an
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Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeutic efficacy. We discuss combination therapies, derivatization, and the use of resveratrol nanoparticles. Interestingly, the combination of resveratrol with established chemotherapeutic drugs has shown promising therapeutic effects on colon cancer (with oxaliplatin), liver cancer (with cisplatin, 5-FU), and gastric cancer (with doxorubicin). On the other hand, derivatizing resveratrol, including hydroxylation, amination, amidation, imidation, methoxylation, prenylation, halogenation, glycosylation, and oligomerization, differentially modifies its bioavailability and could be used for preferential therapeutic outcomes. Moreover, the encapsulation of resveratrol allows its trapping within different forms of shells for targeted therapy. Depending on the nanoparticle used, it can enhance its solubility and absorption, increasing its bioavailability and efficacy. These include polymers, metals, solid lipids, and other nanoparticles that have shown promising preclinical results, adding more “hype” to the research on resveratrol. This review provides a platform to compare the different approaches to allow directed research into better treatment options with resveratrol.
Full article
(This article belongs to the Special Issue Novel Anti-cancer Compounds: Drug Metabolism and Absorption)
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Testing S. sonnei GMMA with and without Aluminium Salt-Based Adjuvants in Animal Models
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Francesca Mancini, Valentina Caradonna, Renzo Alfini, Maria Grazia Aruta, Claudia Giorgina Vitali, Gianmarco Gasperini, Diego Piccioli, Francesco Berlanda Scorza, Omar Rossi and Francesca Micoli
Pharmaceutics 2024, 16(4), 568; https://doi.org/10.3390/pharmaceutics16040568 - 22 Apr 2024
Abstract
Shigellosis is one of the leading causes of diarrheal disease in low- and middle-income countries, particularly in young children, and is more often associated with antimicrobial resistance. Therefore, a preventive vaccine against shigellosis is an urgent medical need. We have proposed Generalised Modules
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Shigellosis is one of the leading causes of diarrheal disease in low- and middle-income countries, particularly in young children, and is more often associated with antimicrobial resistance. Therefore, a preventive vaccine against shigellosis is an urgent medical need. We have proposed Generalised Modules for Membrane Antigens (GMMA) as an innovative delivery system for Shigella sonnei O-antigen, and an Alhydrogel formulation (1790GAHB) has been extensively tested in preclinical and clinical studies. Alhydrogel has been used as an adsorbent agent with the main purpose of reducing potential GMMA systemic reactogenicity. However, the immunogenicity and systemic reactogenicity of this GMMA-based vaccine formulated with or without Alhydrogel have never been compared. In this work, we investigated the potential adjuvant effect of aluminium salt-based adjuvants (Alhydrogel and AS37) on S. sonnei GMMA immunogenicity in mice and rabbits, and we found that S. sonnei GMMA alone resulted to be strongly immunogenic. The addition of neither Alhydrogel nor AS37 improved the magnitude or the functionality of vaccine-elicited antibodies. Interestingly, rabbits injected with either S. sonnei GMMA adsorbed on Alhydrogel or S. sonnei GMMA alone showed a limited and transient body temperature increase, returning to baseline values within 24 h after each vaccination. Overall, immunisation with unadsorbed GMMA did not raise any concern for animal health. We believe that these data support the clinical testing of GMMA formulated without Alhydrogel, which would allow for further simplification of GMMA-based vaccine manufacturing.
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(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases
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Valentina Arrè, Rita Mastrogiacomo, Francesco Balestra, Grazia Serino, Federica Viti, Federica Rizzi, Maria Lucia Curri, Gianluigi Giannelli, Nicoletta Depalo and Maria Principia Scavo
Pharmaceutics 2024, 16(4), 567; https://doi.org/10.3390/pharmaceutics16040567 - 21 Apr 2024
Abstract
Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and
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Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and organ homeostasis. Conversely, in pathological conditions, they significantly contribute to the pathogenesis of gastrointestinal diseases (GIDs). Isolating EVs from patients’ biofluids facilitates the discovery of new biomarkers that have the potential to offer a rapid, cost-effective, and non-invasive method for diagnosing and prognosing specific GIDs. Furthermore, EVs demonstrate considerable therapeutic potential as naturally targeted physiological carriers for the intercellular delivery of therapeutic cargo molecules or as nanoscale tools engineered specifically to regulate physio-pathological conditions or disease progression. Their attributes including safety, high permeability, stability, biocompatibility, low immunogenicity, and homing/tropism capabilities contribute to their promising clinical therapeutic applications. This review will delve into various examples of EVs serving as biomarkers or nanocarriers for therapeutic cargo in the context of GIDs, highlighting their clinical potential for both functional and structural gastrointestinal conditions. The versatile and advantageous properties of EVs position them as promising candidates for innovative therapeutic strategies in advancing personalized medicine approaches tailored to the gastroenteric tract, addressing both functional and structural GIDs.
Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma
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Kyeongjin Seo, Kihwan Hwang, Kyung Mi Nam, Min Ju Kim, Yoon-Kyu Song and Chae-Yong Kim
Pharmaceutics 2024, 16(4), 566; https://doi.org/10.3390/pharmaceutics16040566 - 21 Apr 2024
Abstract
Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in
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Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres (100–300 nm in size) loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than non-specific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study reveals the potential for anti-cancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labeling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier allowing for the precise targeting of tumors. This combination has the potential to produce anti-tumor effects in the active targeted therapy of GBM.
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(This article belongs to the Special Issue Anti-Cancer Drug Delivery Systems)
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Performance Characterisation of the Airvo2TM Nebuliser Adapter in Combination with the Aerogen SoloTM Vibrating Mesh Nebuliser for in Line Aerosol Therapy during High Flow Nasal Oxygen Therapy
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Ronan MacLoughlin and Marc Mac Giolla Eain
Pharmaceutics 2024, 16(4), 565; https://doi.org/10.3390/pharmaceutics16040565 - 20 Apr 2024
Abstract
High flow oxygen (HFO) therapy is a well-established treatment in respiratory disease. Concurrent aerosol delivery can greatly expediate their recovery. The aim of this work was to complete a comprehensive characterisation of one such HFO therapy system, the Airvo2TM, used in
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High flow oxygen (HFO) therapy is a well-established treatment in respiratory disease. Concurrent aerosol delivery can greatly expediate their recovery. The aim of this work was to complete a comprehensive characterisation of one such HFO therapy system, the Airvo2TM, used in combination with the Aerogen SoloTM vibrating mesh nebuliser. Representative adult, infant, and paediatric head models were connected to a breathing simulator via a collection filter placed at the level of the trachea. A tracheostomy interface and nasal cannulas were used to deliver the aerosol. Cannula size and gas flow rate were varied across the full operating range recommended by the manufacturer. The tracheal and emitted doses were quantified via UV-spectrophotometry. The aerosol droplet diameter at the exit of the nares and tracheal interface was measured via cascade impaction. High gas flow rates resulted in low emitted and tracheal doses (%). Nasal cannula size had no significant effect on the tracheal dose (%) available in infant and paediatric models. Higher gas flow rates resulted in smaller aerosol droplets at the exit of the nares and tracheostomy interface. Gas flow rate was found to be the primary parameter affecting aerosol delivery. Thus, gas flow rates should be kept low and where possible, delivered using larger nasal cannulas to maximise aerosol delivery.
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(This article belongs to the Section Drug Delivery and Controlled Release)
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Exploring the Impact of Hepatic Impairment on Pralsetinib Pharmacokinetics
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Kit Wun Kathy Cheung, Yang Tang, Doreen Anders, Teresa Barata, Astrid Scalori, Priya Agarwal, Rucha Sane and Sravanthi Cheeti
Pharmaceutics 2024, 16(4), 564; https://doi.org/10.3390/pharmaceutics16040564 - 20 Apr 2024
Abstract
Pralsetinib is a kinase inhibitor indicated for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer. Pralsetinib is primarily eliminated by the liver and hence hepatic impairment (HI) is likely alter its pharmacokinetics (PK). Mild HI has
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Pralsetinib is a kinase inhibitor indicated for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer. Pralsetinib is primarily eliminated by the liver and hence hepatic impairment (HI) is likely alter its pharmacokinetics (PK). Mild HI has been shown to have minimal impact on the PK of pralsetinib. This hepatic impairment study aimed to determine the pralsetinib PK, safety and tolerability in subjects with moderate and severe HI, as defined by the Child–Pugh and National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification systems, in comparison to subjects with normal hepatic function. Based on the Child–Pugh classification, subjects with moderate and severe HI had similar systemic exposure (area under the plasma concentration time curve from time 0 to infinity [AUC0–∞]) to pralsetinib, with AUC0–∞ geometric mean ratios (GMR) of 1.12 and 0.858, respectively, compared to subjects with normal hepatic function. Results based on the NCI-ODWG classification criteria were comparable; the AUC0–∞ GMR were 1.22 and 0.858, respectively, for subjects with moderate and severe HI per NCI-ODWG versus those with normal hepatic function. These results suggested that moderate and severe hepatic impairment did not have a meaningful impact on the exposure to pralsetinib, thus not warranting a dose adjustment in this population.
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(This article belongs to the Special Issue Advances in Pharmacokinetics and Drug-Drug Interactions)
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Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi
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Victor Passos Gibson, Houda Tahiri, Claudia Gilbert, Chun Yang, Quoc Thang Phan, Xavier Banquy and Pierre Hardy
Pharmaceutics 2024, 16(4), 563; https://doi.org/10.3390/pharmaceutics16040563 - 20 Apr 2024
Abstract
Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention
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Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated by our previous work, here we investigate if the LbL approach could be used to modify the LNP cores formulated with three different ionizable lipids: DODMA, MC3, and DODAP. Additionally, we wondered if more than three layers could be loaded onto LNPs without disrupting their gene transfection ability. Taking advantage of physicochemical analysis, as well as uptake and gene silencing studies, we demonstrate the feasibility of modifying the surface of LNPs with the LbL assembly. Precisely, we successfully modified three different LNPs using the layer-by-layer strategy which abrogated luciferase activity in vitro. Additionally, we constructed a 5×-layered HA-LNP containing the MC3 ionizable lipid which outperformed the 3×-layered counterpart in transfecting miRNA-181-5p to the pediatric GBM cell line, as a proof-of-concept in vitro experiment. The method used herein has been proven reproducible, of easy modification to adapt to different ionizable lipid-containing LNPs, and holds great potential for the translation of RNA-based therapeutic strategies.
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(This article belongs to the Special Issue New Nano-Systems for Imaging, Diagnostics, and Drug Delivery)
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Amount of Dentifrice and Fluoride Concentration Affect the pH and Inorganic Composition of Dual-Species Biofilms of Streptococcus mutans and Candida albicans
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Caio Sampaio, Alberto Carlos Botazzo Delbem, Thayse Yumi Hosida, Ana Vitória Pereira Fernandes, Bruna do Amaral, Leonardo Antônio de Morais, Douglas Roberto Monteiro and Juliano Pelim Pessan
Pharmaceutics 2024, 16(4), 562; https://doi.org/10.3390/pharmaceutics16040562 - 20 Apr 2024
Abstract
This work assessed the influence of the amount of dentifrice and fluoride (F) concentration in the product on the pH and inorganic components of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated with suspensions of fluoride dentifrices containing 550 or
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This work assessed the influence of the amount of dentifrice and fluoride (F) concentration in the product on the pH and inorganic components of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated with suspensions of fluoride dentifrices containing 550 or 1100 ppm of F (550 F or 1100 F, respectively) administered at comparable intensities: (i-1) 550 F/0.08 g or 1100 F/0.04 g; (i-2) 550 F/0.16 g or 1100 F/0.08 g; and (i-3) 550 F/0.32 g or 1100 F/0.16 g. A placebo dentifrice (without NaF, 0.32 g) was used as a negative control. After the last treatment, the biofilm pH was measured and the F, calcium (Ca), and phosphorus (P) concentrations were determined. Data were subjected to an ANOVA/Kruskal–Wallis test, and a Student–Newman–Keuls test. The highest biofilm pH and F concentrations (biomass and fluid) were observed for 1100 F at i-3. Overall, 1100 F resulted in F levels similar to 550 F for i-1 and i-2. In addition, 550 F applied at i-2 and i-3 led to higher F in the biomass/fluid compared to 1100 F applied at i-1 and i-2, respectively. In biomass, the lowest Ca concentrations were observed for 1100 F at i-3. The conclusion drawn is that the treatment intensity holds greater significance as a parameter compared to the concentration of F or the amount of dentifrice when considered individually.
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(This article belongs to the Special Issue Recent Advances in the Prevention and Eradication Strategies for Combating Biofilm-Related Infections)
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Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population
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Gareth I. Owen, Miguel Cordova-Delgado, Bernabé I. Bustos, Leslie C. Cerpa, Pamela Gonzalez, Sebastián Morales-Pison, Benjamín Garcia-Bloj, Marcelo Garrido, Juan Francisco Miquel and Luis A. Quiñones
Pharmaceutics 2024, 16(4), 561; https://doi.org/10.3390/pharmaceutics16040561 - 19 Apr 2024
Abstract
Background: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges
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Background: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry. Methods: To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with p ≤ 0.05 and Bonferroni’s multiple adjustment tests determined statistical differences between allele frequencies. Results: Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase (DPYD) variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 (NUDT15) rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of TMPT gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031–0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene (UGT1A1) rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations. Conclusions: This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.
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(This article belongs to the Special Issue Advances in Pharmacogenomic Studies)
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Host–Guest Complexation of Itraconazole with Cyclodextrins for Bioavailability Enhancement
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Lenuţa-Maria Şuta, Amalia Ridichie, Adriana Ledeţi, Claudia Temereancă, Ionuţ Ledeţi, Delia Muntean, Matilda Rădulescu, Renata-Maria Văruţ, Claudia Watz, Florentin Crăineanu, Denisa Ivan, Gabriela Vlase and Lavinia Stelea
Pharmaceutics 2024, 16(4), 560; https://doi.org/10.3390/pharmaceutics16040560 - 19 Apr 2024
Abstract
Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but
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Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest–host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole–cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.
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(This article belongs to the Special Issue Cyclodextrins in Drug Delivery, 2nd Edition)
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Open AccessArticle
Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis
by
Bálint Krajcsir, Marianna Pócsi, Zsolt Fejes, Béla Nagy, Jr., János Kappelmayer and Ildikó Beke Debreceni
Pharmaceutics 2024, 16(4), 559; https://doi.org/10.3390/pharmaceutics16040559 - 19 Apr 2024
Abstract
BCR-ABL tyrosine kinase inhibitors (TKIs) are effective drugs in the treatment of patients with chronic myeloid leukemia. However, based on clinical studies, ponatinib was associated with the development of thrombotic complications. Since endothelial cells (ECs) regulate blood coagulation, their abnormal phenotype may play
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BCR-ABL tyrosine kinase inhibitors (TKIs) are effective drugs in the treatment of patients with chronic myeloid leukemia. However, based on clinical studies, ponatinib was associated with the development of thrombotic complications. Since endothelial cells (ECs) regulate blood coagulation, their abnormal phenotype may play a role in the development of thrombotic events. We here aimed to investigate the effect of ponatinib on the procoagulant activity of cultured endothelial cells in vitro. Human coronary artery endothelial cells (HCAECs) were incubated with 50, 150, and 1000 nM of ponatinib. Subsequently, phosphatidylserine (PS) exposure and endothelial microvesicles (EMVs) were measured by flow cytometry. In addition, EC- and EMV-dependent thrombin generation was analyzed. To investigate pro-apoptotic effects of ponatinib, the level of Bax and Bcl-xL proteins were studied using Western blot and F3, THBD, and VCAM1 mRNAs were quantified by qPCR. Therapeutic concentrations of ponatinib significantly increased PS expression on ECs and the amount of EMVs which significantly shortened the time parameters of thrombin generation. In addition, these changes were associated with an increased ratio of Bax and Bcl-xL proteins in the presence of the decreased THBD mRNA level. Overall, ponatinib enhances the procoagulant activity of ECs via inducing apoptosis, which may contribute to thrombotic events.
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(This article belongs to the Special Issue Kinase Inhibitor for Cancer Therapy, 2nd Edition)
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Open AccessArticle
ABCG2 Transports the Flukicide Nitroxynil and Affects Its Biodistribution and Secretion into Milk
by
Laura Álvarez-Fernández, Esther Blanco-Paniagua and Gracia Merino
Pharmaceutics 2024, 16(4), 558; https://doi.org/10.3390/pharmaceutics16040558 - 19 Apr 2024
Abstract
The ABCG2 transporter plays a key role in pharmacological and toxicological processes, affecting bioavailability, tissue accumulation and milk secretion of its substrates. This protein is expressed in several biological barriers acting as a protective mechanism against xenobiotic exposure by pumping out a broad
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The ABCG2 transporter plays a key role in pharmacological and toxicological processes, affecting bioavailability, tissue accumulation and milk secretion of its substrates. This protein is expressed in several biological barriers acting as a protective mechanism against xenobiotic exposure by pumping out a broad range of compounds. However, its induced expression during lactation in alveolar cells of mammary gland represents a relevant route for active transport of unwanted chemicals into milk. This work aimed to characterize the involvement of ABCG2 in systemic exposure and milk secretion of the flukicide nitroxynil. Using MDCK–II cells overexpressing the transporter, we showed that nitroxynil is an in vitro substrate of different species variants of ABCG2. Moreover, using wild-type and Abcg2−/− mice, we showed that murine Abcg2 clearly affects plasma levels of nitroxynil. We also reported differences in nitroxynil accumulation in several tissues, with almost 2-fold higher concentration in kidney, small intestine and testis of Abcg2−/− mice. Finally, we proved that nitroxynil secretion into milk was also affected by Abcg2, with a 1.9-fold higher milk concentration in wild-type compared with Abcg2−/− mice. We conclude that ABCG2 significantly impacts nitroxynil biodistribution by regulating its passage across biological barriers.
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(This article belongs to the Special Issue Transport of Drugs through Biological Barriers—an Asset or Risk)
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Open AccessReview
Hypoxia-Activated Theragnostic Prodrugs (HATPs): Current State and Future Perspectives
by
Sankarprasad Bhuniya and Eirinaios I. Vrettos
Pharmaceutics 2024, 16(4), 557; https://doi.org/10.3390/pharmaceutics16040557 - 19 Apr 2024
Abstract
Hypoxia is a significant feature of solid tumors and frequently poses a challenge to the effectiveness of tumor-targeted chemotherapeutics, thereby limiting their anticancer activity. Hypoxia-activated prodrugs represent a class of bio-reductive agents that can be selectively activated in hypoxic compartments to unleash the
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Hypoxia is a significant feature of solid tumors and frequently poses a challenge to the effectiveness of tumor-targeted chemotherapeutics, thereby limiting their anticancer activity. Hypoxia-activated prodrugs represent a class of bio-reductive agents that can be selectively activated in hypoxic compartments to unleash the toxic warhead and thus, eliminate malignant tumor cells. However, their applicability can be further elevated by installing fluorescent modalities to yield hypoxia-activated theragnostic prodrugs (HATPs), which can be utilized for the simultaneous visualization and treatment of hypoxic tumor cells. The scope of this review is to summarize noteworthy advances in recent HATPs, highlight the challenges and opportunities for their further development, and discuss their potency to serve as personalized medicines in the future.
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(This article belongs to the Special Issue Research on Therapeutic Prodrugs for Targeted Cancer Therapy)
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High Manganese Content of Lipid NanoMn (LNM) by Microfluidic Technology for Enhancing Anti-Tumor Immunity
by
Jiawei Sun, Jingjing Gong, Lidong Gong, Chuanda Zhu, Longhao Li-Yang, Jingya Wang, Yuanyuan Yang, Shiming Zhang, Silu Liu, Ji-Jun Fu and Pengcheng Xu
Pharmaceutics 2024, 16(4), 556; https://doi.org/10.3390/pharmaceutics16040556 - 19 Apr 2024
Abstract
Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design
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Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.
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(This article belongs to the Special Issue Advanced Nanopharmaceutics for Anticancer Therapy)
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Darunavir Nanoformulation Suppresses HIV Pathogenesis in Macrophages and Improves Drug Delivery to the Brain in Mice
by
Lina Zhou, Sandip Godse, Namita Sinha, Sunitha Kodidela, Udai Singh and Santosh Kumar
Pharmaceutics 2024, 16(4), 555; https://doi.org/10.3390/pharmaceutics16040555 - 19 Apr 2024
Abstract
Although antiretroviral therapy (ART) can suppress peripheral HIV, patients still suffer from neuroHIV due to insufficient levels of ART drugs in the brain. Hence, this study focuses on developing a poly lactic-co-glycolic acid (PLGA) nanoparticle-based ART drug delivery system for darunavir (DRV) using
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Although antiretroviral therapy (ART) can suppress peripheral HIV, patients still suffer from neuroHIV due to insufficient levels of ART drugs in the brain. Hence, this study focuses on developing a poly lactic-co-glycolic acid (PLGA) nanoparticle-based ART drug delivery system for darunavir (DRV) using an intranasal route that can overcome the limitation of drug metabolic stability and blood–brain barrier (BBB) permeability. The physicochemical properties of PLGA-DRV were characterized. The results indicated that PLGA-DRV formulation inhibits HIV replication in U1 macrophages directly and in the presence of the BBB without inducing cytotoxicity. However, the PLGA-DRV did not inhibit HIV replication more than DRV alone. Notably, the total antioxidant capacity remained unchanged upon treatment with both DRV or PLGA-DRV in U1 cells. Compared to DRV alone, PLGA-DRV further decreased reactive oxygen species, suggesting a decrease in oxidative stress by the formulation. Oxidative stress is generally increased by HIV infection, leading to increased inflammation. Although the PLGA-DRV formulation did not further reduce the inflammatory response, the formulation did not provoke an inflammatory response in HIV-infected U1 macrophages. As expected, in vitro experiments showed higher DRV permeability by PLGA-DRV than DRV alone to U1 macrophages. Importantly, in vivo experiments, especially using intranasal administration of PLGA-DRV in wild-type mice, demonstrated a significant increase in the brain-to-plasma ratio of DRV compared to the free DRV. Overall, findings from this study attest to the potential of the PLGA-DRV nanoformulation in reducing HIV pathogenesis in macrophages and enhancing drug delivery to the brain, offering a promising avenue for treating HIV-related neurological disorders.
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(This article belongs to the Special Issue Next Generation of PLGA-Based Nanoparticles as Drug Delivery Systems for Biomedical Applications)
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