Pharmaceutics最新文献

{"title":"Glucose Metabolism-Modifying Natural Materials for Potential Feed Additive Development","authors":"Wei-Chih Lin, Boon-Chin Hoe, Xianming Li, Daizheng Lian, Xiaowei Zeng","doi":"10.3390/pharmaceutics16091208","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091208","url":null,"abstract":"Glucose, a primary energy source derived from animals’ feed ration, is crucial for their growth, production performance, and health. However, challenges such as metabolic stress, oxidative stress, inflammation, and gut microbiota disruption during animal production practices can potentially impair animal glucose metabolism pathways. Phytochemicals, probiotics, prebiotics, and trace minerals are known to change the molecular pathway of insulin-dependent glucose metabolism and improve glucose uptake in rodent and cell models. These compounds, commonly used as animal feed additives, have been well studied for their ability to promote various aspects of growth and health. However, their specific effects on glucose uptake modulation have not been thoroughly explored. This article focuses on glucose metabolism is on discovering alternative non-pharmacological treatments for diabetes in humans, which could have significant implications for developing feed additives that enhance animal performance by promoting insulin-dependent glucose metabolism. This article also aims to provide information about natural materials that impact glucose uptake and to explore their potential use as non-antibiotic feed additives to promote animal health and production. Further exploration of this topic and the materials involved could provide a basis for new product development and innovation in animal nutrition.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Applications of Amphiphilic Copolymers in Drug Release Systems for Skin Treatment","authors":"Yudy Vanessa Cardona, Lizeth Geraldine Muñoz, Daniela Gutierrez Cardozo, Andrés Felipe Chamorro","doi":"10.3390/pharmaceutics16091203","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091203","url":null,"abstract":"Amphiphilic copolymers (ACs) are versatile systems with self-assembling and aggregating properties, enabling the formation of nanomaterials (NMs) such as micelles, vesicles, nanocapsules, and nanogels. These materials have been extensively explored for the delivery of various drugs and active compounds, enhancing the solubility and permeation of poorly water-soluble drugs into skin tissue. This improvement facilitates the treatment of skin diseases, including chronic conditions like cancer, as well as infections caused by bacteria, fungi, and viruses. This review summarizes recent applications of ACs in skin treatment, with a particular focus on their use in anti-cancer drug therapy. It covers the synthesis, classification, and characterization of ACs using various experimental techniques. Additionally, it discusses recent research on different drug delivery pathways using ACs, including encapsulation efficiency, release behavior, characteristics, applications, and responses to various chemical and physical stimuli (both in vivo and in vitro). Furthermore, this review provides a comprehensive analysis of the effects of ACs NMs on several skin diseases, highlighting their potential as alternative treatments.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Extracellular Vesicles Generated from the Integra CELLine Culture System and Their Endocytic Pathways for Intracellular Drug Delivery","authors":"Tianjiao Geng, Lei Tian, Song Yee Paek, Euphemia Leung, Lawrence W. Chamley, Zimei Wu","doi":"10.3390/pharmaceutics16091206","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091206","url":null,"abstract":"Extracellular vesicles (EVs) have attracted great attention as promising intracellular drug delivery carriers. While the endocytic pathways of small EVs (sEVs, <200 nm) have been reported, there is limited understanding of large EVs (lEVs, >200 nm), despite their potential applications for drug delivery. Additionally, the low yield of EVs during isolation remains a major challenge in their application. Herein, we aimed to compare the endocytic pathways of sEVs and lEVs using MIA PaCa-2 pancreatic cancer cell-derived EVs as models and to explore the efficiency of their production. The cellular uptake of EVs by MIA PaCa-2 cells was assessed and the pathways were investigated with the aid of endocytic inhibitors. The yield and protein content of sEVs and lEVs from the Integra CELLine culture system and the conventional flasks were compared. Our findings revealed that both sEVs and lEVs produced by the Integra CELLine system entered their parental cells via multiple routes, including caveolin-mediated endocytosis, clathrin-mediated endocytosis, and actin-dependent phagocytosis or macropinocytosis. Notably, caveolin- and clathrin-mediated endocytosis were more prominent in the uptake of sEVs, while actin-dependent phagocytosis and macropinocytosis were significant for both sEVs and lEVs. Compared with conventional flasks, the Integra CELLine system demonstrated a 9-fold increase in sEVs yield and a 6.5-fold increase in lEVs yield, along with 3- to 4-fold higher protein content per 1010 EVs. Given that different endocytic pathways led to distinct intracellular trafficking routes, this study highlights the unique potentials of sEVs and lEVs for intracellular cargo delivery. The Integra CELLine proves to be a highly productive and cost-effective system for generating EVs with favourable properties for drug delivery.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Chitosan in Prevention and Treatment Strategies of Infectious Diseases","authors":"Genada Sinani, Melike Sessevmez, Sevda Şenel","doi":"10.3390/pharmaceutics16091201","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091201","url":null,"abstract":"Chitosan is the most commonly investigated functional cationic biopolymer in a wide range of medical applications due to its promising properties such as biocompatibility, biodegradability, and bioadhesivity, as well as its numerous bioactive properties. Within the last three decades, chitosan and its derivatives have been investigated as biomaterials for drug and vaccine delivery systems, besides for their bioactive properties. Due to the functional groups in its structure, it is possible to tailor the delivery systems with desired properties. There has been a great interest in the application of chitosan-based systems also for the prevention and treatment of infectious diseases, specifically due to their antimicrobial, antiviral, and immunostimulatory effects. In this review, recent applications of chitosan in the prevention and treatment of infectious diseases are reviewed, and possibilities and limitations with regards to technical and regulatory aspects are discussed. Finally, the future perspectives on utilization of chitosan as a biomaterial are discussed.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Barriers for Drug Delivery and Development of Innovative Therapeutic Approaches in HIV, Pancreatic Cancer, and Hemophilia A/B","authors":"Emre Basar, Henry Mead, Bennett Shum, Ingrid Rauter, Cihan Ay, Adriane Skaletz-Rorowski, Norbert H. Brockmeyer","doi":"10.3390/pharmaceutics16091207","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091207","url":null,"abstract":"Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease’s pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which—upon effective drug delivery to their target cells—allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Performance of Co-Assembled Hybrid Nanocarriers: Moving towards the Formation of a Multifunctional Lipid/Random Copolymer Nanoplatform","authors":"Efstathia Triantafyllopoulou, Diego Romano Perinelli, Aleksander Forys, Pavlos Pantelis, Vassilis G. Gorgoulis, Nefeli Lagopati, Barbara Trzebicka, Giulia Bonacucina, Georgia Valsami, Natassa Pippa, Stergios Pispas","doi":"10.3390/pharmaceutics16091204","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091204","url":null,"abstract":"Despite the appealing properties of random copolymers, the use of these biomaterials in association with phospholipids is still limited, as several aspects of their performance have not been investigated. The aim of this work is the formulation of lipid/random copolymer platforms and the comprehensive study of their features by multiple advanced characterization techniques. Both biomaterials are amphiphilic, including two phospholipids (1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)) and a statistical copolymer of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA). We examined the design parameters, including the lipid composition, the % comonomer ratio, and the lipid-to-polymer ratio that could be critical for their behavior. The structures were also probed in different conditions. To the best of the authors’ knowledge, this is the first time that P(OEGMA-co-DIPAEMA)/lipid hybrid colloidal dispersions have been investigated from a membrane mechanics, biophysical, and morphological perspective. Among other parameters, the copolymer architecture and the hydrophilic to hydrophobic balance are deemed fundamental parameters for the biomaterial co-assembly, having an impact on the membrane’s fluidity, morphology, and thermodynamics. Exploiting their unique characteristics, the most promising candidates were utilized for methotrexate (MTX) loading to explore their encapsulation capability and potential antitumor efficacy in vitro in various cell lines.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancements in Gallic Acid-Based Drug Delivery: Applications, Clinical Trials, and Future Directions","authors":"Ranjit K. Harwansh, Rohitas Deshmukh, Vijay Pratap Shukla, Dignesh Khunt, Bhupendra Gopalbhai Prajapati, Summya Rashid, Nemat Ali, Gehan M. Elossaily, Vijendra Kumar Suryawanshi, Arun Kumar","doi":"10.3390/pharmaceutics16091202","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091202","url":null,"abstract":"Gallic acid (GA) is a well-known herbal bioactive compound found in many herbs and foods like tea, wine, cashew nuts, hazelnuts, walnuts, plums, grapes, mangoes, blackberries, blueberries, and strawberries. GA has been reported for several pharmacological activities, such as antioxidant, inflammatory, antineoplastic, antimicrobial, etc. Apart from its incredible therapeutic benefits, it has been associated with low permeability and bioavailability issues, limiting their efficacy. GA belongs to BCS (Biopharmaceutics classification system) class III (high solubility and low probability). In this context, novel drug delivery approaches played a vital role in resolving these GA issues. Nanocarrier systems help improve drug moiety’s physical and chemical stability by encapsulating them into a lipidic or polymeric matrix or core system. In this regard, researchers have developed a wide range of nanocarrier systems for GA, including liposomes, transfersomes, niosomes, dendrimers, phytosomes, micelles, nanoemulsions, metallic nanoparticles, solid lipid nanoparticles (SLNs), nanoparticles, nanostructured lipid carriers, polymer conjugates, etc. In the present review, different search engines like Scopus, PubMed, ScienceDirect, and Google Scholar have been referred to for acquiring recent information on the theme of the work. Therefore, this review paper aims to emphasize several novel drug delivery systems, patents, and clinical updates of GA.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of Non-Canonical Ferroptosis by Targeting Clusters Suppresses Glioblastoma","authors":"Kai Cao, Liyuan Xue, Kaidi Luo, Wendi Huo, Panpan Ruan, Dongfang Xia, Xiuxiu Yao, Wencong Zhao, Liang Gao, Xueyun Gao","doi":"10.3390/pharmaceutics16091205","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091205","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most aggressive brain tumor. There is a pressing need to develop novel treatment strategies due to the poor targeting effect of current therapeutics. Here, a gold cluster coated with optimized GBM-targeting peptide is engineered, namely NA. NA can efficiently target GBM both in vitro and in vivo. Interestingly, the uptake of NA significantly sensitizes GBM cells to ferroptosis, a form of programmed cell death that can bypass the tumor resistance to apoptosis. This effect is exerted through regulating the HO-1-dependent iron ion metabolism, which is the non-canonical pathway of ferroptosis. The combined treatment of a ferroptosis inducer and NA profoundly inhibited tumor growth in both the GBM spheroid model and a syngeneic mouse model with enhanced ferroptosis levels and excellent biosafety. Importantly, the infiltration of tumoricidal lymphocytes is also significantly increased within tumor. Therefore, NA presents a potential novel nanomaterial-based strategy for GBM treatment.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Implications of Co-Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer","authors":"Mafalda Calheiros-Lobo, João P. N. Silva, Bárbara Pinto, Luís Monteiro, Patrícia M. A. Silva, Hassan Bousbaa","doi":"10.3390/pharmaceutics16091196","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091196","url":null,"abstract":"Head and neck cancer (HNC), the sixth most common cancer worldwide, is increasing in incidence, with oral squamous cell carcinoma (OSCC) as the predominant subtype. OSCC mainly affects middle-aged to elderly males, often occurring on the posterior lateral border of the tongue, leading to significant disfigurement and functional impairments, such as swallowing and speech difficulties. Despite advancements in understanding OSCC’s genetic and epigenetic variations, survival rates for advanced stages remain low, highlighting the need for new treatment options. Primary treatment includes surgery, often combined with radiotherapy (RT) and chemotherapy (CT). Cetuximab-based chemotherapy, targeting the overexpressed epidermal growth factor receptor (EGFR) in 80–90% of HNCs, is commonly used but correlates with poor prognosis. Additionally, monopolar spindle 1 (MPS1), a spindle assembly checkpoint (SAC) component, is a significant target due to its role in genomic fidelity during mitosis and its overexpression in several cancers. This review explores EGFR and MPS1 as therapeutic targets in HNC, analyzing their molecular mechanisms and the effects of their inhibition on cancer cells. It also highlights the promise of combinatorial approaches, such as microtubule-targeting agents (MTAs) and antimitotic agents, in improving HNC therapies, patient outcomes, and survival rates.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Nanoparticles as Non-Viral Vectors for Efficient Delivery of CRISPR/Cas9","authors":"Minse Kim, Youngwoo Hwang, Seongyu Lim, Hyeon-Ki Jang, Hyun-Ouk Kim","doi":"10.3390/pharmaceutics16091197","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091197","url":null,"abstract":"The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is a gene-editing technology. Nanoparticle delivery systems have attracted attention because of the limitations of conventional viral vectors. In this review, we assess the efficiency of various nanoparticles, including lipid-based, polymer-based, inorganic, and extracellular vesicle-based systems, as non-viral vectors for CRISPR/Cas9 delivery. We discuss their advantages, limitations, and current challenges. By summarizing recent advancements and highlighting key strategies, this review aims to provide a comprehensive overview of the role of non-viral delivery systems in advancing CRISPR/Cas9 technology for clinical applications and gene therapy.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}