Pub Date : 2024-09-11DOI: 10.3390/pharmaceutics16091195
Suellen Christtine da Costa Sanches, Lindalva Maria de Meneses Costa Ferreira, Rayanne Rocha Pereira, Desireé Gyles Lynch, Ingryd Nayara de Farias Ramos, André Salim Khayat, José Otávio Carrera Silva-Júnior, Alessandra Rossi, Roseane Maria Ribeiro-Costa
Organogels are semi-solid pharmaceutical forms whose dispersing phase is an organic liquid, for example, an oil, such as acai oil, immobilized by a three-dimensional network formed by the gelling agent. Organogels are being highlighted as innovative release systems for cosmetic active ingredients such as hyaluronic acid for topical applications. Acai oil was evaluated for its physicochemical parameters, fatty acid composition, lipid quality index, spectroscopic pattern (Attenuated total reflectance Fourier Transform Infrared Spectroscopy), thermal behavior, total phenolic, total flavonoids, and total carotenoids and β-carotene content. The effectiveness of the organogel incorporated with hyaluronic acid (OG + HA) was evaluated through ex vivo permeation and skin retention tests, in vitro tests by Attenuated total reflectance Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The physicochemical analyses highlighted that the acai oil exhibited quality standards in agreement with the regulatory bodies. Acai oil also showed high antioxidant capacity, which was correlated with the identified bioactive compounds. The cytotoxicity tests demonstrated that the formulation OG + HA does not release toxic substances into the biological environment that could impede cell growth, adhesion, and efficacy. In vitro and ex vivo analyses demonstrated that after 6 h of application, OG + HA presented a high level of hydration, thermal protection and release of HA. Thus, it can be concluded that the OG + HA formulation has the potential for physical–chemical applications, antioxidant quality, and potentially promising efficacy for application in the cosmetic areas.
有机凝胶是一种半固体药物形式，其分散相为有机液体，如油，如巴西莓油，被胶凝剂形成的三维网络固定。有机凝胶作为化妆品活性成分（如用于局部应用的透明质酸）的创新释放系统而备受关注。对巴西莓油的理化参数、脂肪酸组成、脂质指数、光谱模式（衰减全反射傅立叶变换红外光谱）、热行为、总酚、总类黄酮、总类胡萝卜素和β-胡萝卜素含量进行了评估。通过体外渗透和皮肤保留测试、体外tentenuated total reflectance Fourier Transform Infrared Spectroscopy 和差示扫描量热法测试，对添加了透明质酸（OG + HA）的有机凝胶的功效进行了评估。理化分析结果表明，巴西莓油符合监管机构的质量标准。巴西莓油还显示出很高的抗氧化能力，这与已确定的生物活性化合物有关。细胞毒性测试表明，OG + HA 配方不会向生物环境释放有毒物质，从而阻碍细胞的生长、粘附和功效。体外和体内分析表明，涂抹 6 小时后，OG + HA 具有较高的水合作用、热保护作用和 HA 释放作用。因此，可以得出这样的结论：OG + HA 配方具有物理化学应用潜力、抗氧化质量以及在化妆品领域应用的潜在功效。
{"title":"Acai Oil-Based Organogel Containing Hyaluronic Acid for Topical Cosmetic: In Vitro and Ex Vivo Assessment","authors":"Suellen Christtine da Costa Sanches, Lindalva Maria de Meneses Costa Ferreira, Rayanne Rocha Pereira, Desireé Gyles Lynch, Ingryd Nayara de Farias Ramos, André Salim Khayat, José Otávio Carrera Silva-Júnior, Alessandra Rossi, Roseane Maria Ribeiro-Costa","doi":"10.3390/pharmaceutics16091195","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091195","url":null,"abstract":"Organogels are semi-solid pharmaceutical forms whose dispersing phase is an organic liquid, for example, an oil, such as acai oil, immobilized by a three-dimensional network formed by the gelling agent. Organogels are being highlighted as innovative release systems for cosmetic active ingredients such as hyaluronic acid for topical applications. Acai oil was evaluated for its physicochemical parameters, fatty acid composition, lipid quality index, spectroscopic pattern (Attenuated total reflectance Fourier Transform Infrared Spectroscopy), thermal behavior, total phenolic, total flavonoids, and total carotenoids and β-carotene content. The effectiveness of the organogel incorporated with hyaluronic acid (OG + HA) was evaluated through ex vivo permeation and skin retention tests, in vitro tests by Attenuated total reflectance Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The physicochemical analyses highlighted that the acai oil exhibited quality standards in agreement with the regulatory bodies. Acai oil also showed high antioxidant capacity, which was correlated with the identified bioactive compounds. The cytotoxicity tests demonstrated that the formulation OG + HA does not release toxic substances into the biological environment that could impede cell growth, adhesion, and efficacy. In vitro and ex vivo analyses demonstrated that after 6 h of application, OG + HA presented a high level of hydration, thermal protection and release of HA. Thus, it can be concluded that the OG + HA formulation has the potential for physical–chemical applications, antioxidant quality, and potentially promising efficacy for application in the cosmetic areas.","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":"142216096","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}
Pub Date : 2024-09-11DOI: 10.3390/pharmaceutics16091194
Mohamed Skiba, Valentin Lefébure, Frederic Bounoure, Nicolas Milon, Michael Thomas, Herve Lefebvre, Lahiani-Skiba Malika
Drug Delivery Systems (DDSs) of known drugs are prominent candidates for new and more effective treatments of various diseases, as they may increase drug solubility, dissolution velocity, and bioavailability. Mitotane (o,p′-dichlorodimethyl dichloroethane [o,p′-DDD]) is used for the treatment of adrenocortical cancer and, occasionally, Cushing’s syndrome. However, the efficacy of mitotane is limited by its low oral bioavailability, caused by its extremely poor aqueous solubility. This research explores the development of a new powder self-emulsifying drug delivery system (P-SEDDS) for mitotane to improve its oral bioavailability. The study focuses on the new concept of a mitotane-loaded P-SEDDS to overcome the challenges associated with its limited solubility and high logP, thereby improving its therapeutic efficacy, reducing off-target toxicity, and avoiding first-pass metabolism. The P-SEDDS formulations were meticulously designed using only α-cyclodextrin and oil, with the goal of achieving a stable and efficient P-SEDDS. The optimized formulation was characterized for pharmaceutical properties, and its pharmacokinetic behavior was examined in rats. The results demonstrated a significant enhancement in the bioavailability of mitotane when delivered through the P-SEDDS, attributed to the increased dissolution velocity and improved absorption of the poorly water-soluble drug. The results suggest that a mitotane-loaded P-SEDDS has distinctly enhanced in vitro and in vivo performance compared with conventional mitotane formulations (Lysodren®), which leads to the conclusion that the P-SEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poorly aqueous-soluble ingredients.
{"title":"Powder Self-Emulsifying Drug Delivery System for Mitotane: In Vitro and In Vivo Evaluation","authors":"Mohamed Skiba, Valentin Lefébure, Frederic Bounoure, Nicolas Milon, Michael Thomas, Herve Lefebvre, Lahiani-Skiba Malika","doi":"10.3390/pharmaceutics16091194","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091194","url":null,"abstract":"Drug Delivery Systems (DDSs) of known drugs are prominent candidates for new and more effective treatments of various diseases, as they may increase drug solubility, dissolution velocity, and bioavailability. Mitotane (o,p′-dichlorodimethyl dichloroethane [o,p′-DDD]) is used for the treatment of adrenocortical cancer and, occasionally, Cushing’s syndrome. However, the efficacy of mitotane is limited by its low oral bioavailability, caused by its extremely poor aqueous solubility. This research explores the development of a new powder self-emulsifying drug delivery system (P-SEDDS) for mitotane to improve its oral bioavailability. The study focuses on the new concept of a mitotane-loaded P-SEDDS to overcome the challenges associated with its limited solubility and high logP, thereby improving its therapeutic efficacy, reducing off-target toxicity, and avoiding first-pass metabolism. The P-SEDDS formulations were meticulously designed using only α-cyclodextrin and oil, with the goal of achieving a stable and efficient P-SEDDS. The optimized formulation was characterized for pharmaceutical properties, and its pharmacokinetic behavior was examined in rats. The results demonstrated a significant enhancement in the bioavailability of mitotane when delivered through the P-SEDDS, attributed to the increased dissolution velocity and improved absorption of the poorly water-soluble drug. The results suggest that a mitotane-loaded P-SEDDS has distinctly enhanced in vitro and in vivo performance compared with conventional mitotane formulations (Lysodren®), which leads to the conclusion that the P-SEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poorly aqueous-soluble ingredients.","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":"142216095","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}
Pub Date : 2024-09-11DOI: 10.3390/pharmaceutics16091193
Marija M. Babić Radić
The significant progress in design and engineering of advanced hydrogels for biomedical applications is fundamentally driven by the increasing complexity and specificity of challenges in the biomedical field [...]
{"title":"Editorial on Special Issue “Recent Advances in Hydrogels for Biomedical Applications”","authors":"Marija M. Babić Radić","doi":"10.3390/pharmaceutics16091193","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091193","url":null,"abstract":"The significant progress in design and engineering of advanced hydrogels for biomedical applications is fundamentally driven by the increasing complexity and specificity of challenges in the biomedical field [...]","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":"142216094","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}
Pub Date : 2024-09-09DOI: 10.3390/pharmaceutics16091191
Cédric Carrié, Jesse Butruille, Sophie Maingault, Alexandre Lannou, Vincent Dubuisson, Laurent Petit, Matthieu Biais, Dominique Breilh
Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100%fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Results: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Conclusions: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%.
{"title":"Pharmacokinetics of Piperacillin–Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation","authors":"Cédric Carrié, Jesse Butruille, Sophie Maingault, Alexandre Lannou, Vincent Dubuisson, Laurent Petit, Matthieu Biais, Dominique Breilh","doi":"10.3390/pharmaceutics16091191","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091191","url":null,"abstract":"Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100%fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Results: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Conclusions: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216099","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}
Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.
尽管硝氟酸（NA）是最常用的非甾体抗炎药物之一，但它的溶解性差、生物利用度低、不良反应大。为了解决这些局限性，NA 与环糊精（CD）的复配是一种很有前景的策略。然而，将 CD 与 NA 等低分子量药物络合会导致低 CE。本研究探讨了NA与2-羟丙基-β-环糊精（2HP-β-CD）包合复合物的开发，包括将NA转化为其钠盐（NAs）和添加羟丙基甲基纤维素（HPMC）对复合物形成的影响。利用共蒸发溶剂法和冷冻干燥法制备了包合物，并通过相溶解度研究确定了它们的CE和Ks。利用傅立叶变换红外光谱（FT-IR）、扫描电镜（DSC）、电子显微镜（SEM）、X 射线衍射（XRD）、激光光散射（DLS）、紫外可见光谱（UV-Vis）、1H-核磁共振（1H-NMR）和 1H-ROESY 等理化分析对复合物进行了表征。此外，还对复合物的溶解曲线进行了评估。分析结果表明，所有体系都形成了复合物，显示出药物与环糊精之间的相互作用、无定形药物状态、形态变化以及溶解度和溶解曲线的改善。NAs-2HP-β-CD-HPMC 复合物的 CE 值和 Ks 值最高，主客体摩尔比为 1:1，溶解情况最好。结果表明，NAs-2HP-β-CD-HPMC 复合物具有递送 NA 的潜力，可提高 NA 的疗效并减少副作用。
{"title":"Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile","authors":"Zohra Bouchekhou, Amel Hadj Ziane-Zafour, Florentina Geanina Lupascu, Bianca-Ștefania Profire, Alina Nicolescu, Denisse-Iulia Bostiog, Florica Doroftei, Ioan-Andrei Dascalu, Cristian-Dragoș Varganici, Mariana Pinteala, Lenuta Profire, Tudor Pinteala, Bachir Bouzid","doi":"10.3390/pharmaceutics16091190","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091190","url":null,"abstract":"Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216098","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}
Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.
{"title":"Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies","authors":"Rui Luo, Huihui Xu, Qiaoni Lin, Jiaying Chi, Tingzhi Liu, Bingrui Jin, Jiayu Ou, Zejun Xu, Tingting Peng, Guilan Quan, Chao Lu","doi":"10.3390/pharmaceutics16091188","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091188","url":null,"abstract":"Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215962","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}
Pub Date : 2024-09-08DOI: 10.3390/pharmaceutics16091189
Su Yeon Lim, Luna Kim, Hongbin Kim, Jeong-Ann Park, Jina Yun, Kwang Suk Lim
While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells. Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody–drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells. Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment.
虽然传统的联合抗癌疗法已显示出良好的效果，但人们对开发创新方法来增强和整合化疗和免疫疗法仍有浓厚的兴趣。本研究介绍了一种基于重组融合蛋白的细胞表面修饰系统，它能将化疗和免疫疗法协同结合成单一靶向化疗-免疫疗法方法。由抗体特异性结合域和细胞穿透域组成的细胞表面修饰蛋白通过与免疫细胞表面的抗体结合，迅速将免疫细胞转化为化学免疫疗法。我们的系统利用一种无创、无毒、无化学修饰和结合的方法，通过将靶向细胞毒性药物瞬时导入免疫细胞，从而均匀地转化免疫细胞。经表面改造的免疫细胞负载有抗体-药物共轭物（ADCs），能显著抑制靶肿瘤的生长，增强对癌细胞的靶向清除能力。因此，经细胞表面修饰蛋白修饰的 NK 细胞可望结合 ADCs 实现靶向癌细胞识别、化疗和免疫治疗的综合效果，从而提高对癌症的疗效。这种策略可以高效、快速地制备治疗各种癌症的先进化学免疫疗法，为提高癌症治疗效果提供了巨大潜力。
{"title":"Synergistic Chemo-Immunotherapy: Recombinant Fusion Protein-Based Surface Modification of NK Cell for Targeted Cancer Treatment","authors":"Su Yeon Lim, Luna Kim, Hongbin Kim, Jeong-Ann Park, Jina Yun, Kwang Suk Lim","doi":"10.3390/pharmaceutics16091189","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091189","url":null,"abstract":"While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells. Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody–drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells. Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215963","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}
Pub Date : 2024-09-07DOI: 10.3390/pharmaceutics16091183
Lucas Sejournet, Thibaud Mathis, Victor Vermot-Desroches, Rita Serra, Ines Fenniri, Philippe Denis, Laurent Kodjikian
Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.
糖尿病黄斑水肿（DME）是糖尿病视网膜病变的常见并发症。玻璃体内注射治疗对大多数病例有效，但患者的治疗负担较重。这意味着需要长期治疗，如植入氟西诺龙醋酸酯（FAc）。我们对基础科学、药理学和临床数据进行了回顾，以提供 2024 年 FAc 植入物的最新观点。虽然 FAc 植入物的耐受性普遍良好，但它也与眼压过高和白内障有关，因此建议患者谨慎使用。通过综合这些领域的信息，可以获得全面的评估结果，有助于在使用 FAc 植入体治疗 DME 方面做出明智的决策。本综述的主要目的是为临床医生提供指导，帮助他们了解如何在二重性视网膜病变患者中引入和使用FAc植入体。
{"title":"Efficacy and Safety of Fluocinolone Acetonide Implant in Diabetic Macular Edema: Practical Guidelines from Reference Center","authors":"Lucas Sejournet, Thibaud Mathis, Victor Vermot-Desroches, Rita Serra, Ines Fenniri, Philippe Denis, Laurent Kodjikian","doi":"10.3390/pharmaceutics16091183","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091183","url":null,"abstract":"Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215966","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}
Pub Date : 2024-09-07DOI: 10.3390/pharmaceutics16091182
Milica Lukić, Ana Ćirić, Dragana D. Božić, Jelena Antić Stanković, Đorđe Medarević, Zoran Maksimović
Agricultural waste is underutilized, and sometimes burning them has a negative impact on the environment and human health. This research investigates the untapped potential of extracts from maize, wheat and sunflower waste as natural materials for cutaneous, specifically, cosmetic application. The possibility of incorporating lipid and ethanol extracts from wheat, maize, and sunflower into creams was investigated together with their potential contribution to the structural and functional properties of the topical formulations. Results of the physicochemical characterization show that investigated extracts can be successfully incorporated into creams with satisfactory stability. All extracts showed a desirable safety profile and good antimicrobial activity against various microorganisms. Lipid extracts have proven to be promising structural ingredients of the oil phase, contributing to the spreadability, occlusivity, and emollient effect. Ethanol extracts influenced washability and stickiness of the formulation and could be considered as prospective ingredients in self-preserving formulations. The extracts affected the sensory properties of the creams, mainly the smell and color. These results suggest that the extracts from wheat, maize, and sunflower waste could be used as multifunctional natural ingredients for cosmetic formulations which can replace less sustainable raw materials. This also represents a valorization of waste and is in line with broader sustainability goals.
{"title":"Extracts from Wheat, Maize, and Sunflower Waste as Natural Raw Materials for Cosmetics: Value-Added Products Reaching Sustainability Goals","authors":"Milica Lukić, Ana Ćirić, Dragana D. Božić, Jelena Antić Stanković, Đorđe Medarević, Zoran Maksimović","doi":"10.3390/pharmaceutics16091182","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091182","url":null,"abstract":"Agricultural waste is underutilized, and sometimes burning them has a negative impact on the environment and human health. This research investigates the untapped potential of extracts from maize, wheat and sunflower waste as natural materials for cutaneous, specifically, cosmetic application. The possibility of incorporating lipid and ethanol extracts from wheat, maize, and sunflower into creams was investigated together with their potential contribution to the structural and functional properties of the topical formulations. Results of the physicochemical characterization show that investigated extracts can be successfully incorporated into creams with satisfactory stability. All extracts showed a desirable safety profile and good antimicrobial activity against various microorganisms. Lipid extracts have proven to be promising structural ingredients of the oil phase, contributing to the spreadability, occlusivity, and emollient effect. Ethanol extracts influenced washability and stickiness of the formulation and could be considered as prospective ingredients in self-preserving formulations. The extracts affected the sensory properties of the creams, mainly the smell and color. These results suggest that the extracts from wheat, maize, and sunflower waste could be used as multifunctional natural ingredients for cosmetic formulations which can replace less sustainable raw materials. This also represents a valorization of waste and is in line with broader sustainability goals.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215964","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}
Pub Date : 2024-09-07DOI: 10.3390/pharmaceutics16091185
Annalisa Di Rienzo, Lisa Marinelli, Marilisa Pia Dimmito, Eleonora Chiara Toto, Antonio Di Stefano, Ivana Cacciatore
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field.
{"title":"Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems","authors":"Annalisa Di Rienzo, Lisa Marinelli, Marilisa Pia Dimmito, Eleonora Chiara Toto, Antonio Di Stefano, Ivana Cacciatore","doi":"10.3390/pharmaceutics16091185","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091185","url":null,"abstract":"Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215972","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}
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