Pub Date : 2024-11-01Epub Date: 2024-10-07DOI: 10.1080/10837450.2024.2410448
Bahgat Fayed, Shanshan Luo, Alaa Eldeen B Yassin
Erythropoietin (EPO) is a pivotal hormone that regulates red blood cell production, predominantly synthesized by the kidneys and also produced by the liver. Since the introduction of recombinant human EPO (rh-EPO) in 1989 through recombinant DNA technology, the therapeutic landscape for anemia has been improved. rh-EPO's market expansion has been substantial, with its application extending across various conditions such as chronic kidney disease, cancer-related anemia, and other disorders. Despite its success, significant concerns remain regarding the stability of EPO, which is critical for preserving its biological activity and ensuring therapeutic efficacy under diverse environmental conditions. Instability issues, including degradation and loss of biological activity, challenge both drug development and treatment outcomes. Factors contributing to EPO instability include temperature fluctuations, light exposure, and interactions with other substances. To overcome these challenges, pharmaceutical research has focused on developing innovative strategies such as stabilizing agents, advanced formulation techniques, and optimized storage conditions. This review article explores the multifaceted aspects of EPO stability, examining the impact of instability on clinical efficacy and drug development. It also provides a comprehensive review of current stabilization strategies, including the use of excipients, lyophilization, and novel delivery systems.
{"title":"Challenges and recent advances in erythropoietin stability.","authors":"Bahgat Fayed, Shanshan Luo, Alaa Eldeen B Yassin","doi":"10.1080/10837450.2024.2410448","DOIUrl":"10.1080/10837450.2024.2410448","url":null,"abstract":"<p><p>Erythropoietin (EPO) is a pivotal hormone that regulates red blood cell production, predominantly synthesized by the kidneys and also produced by the liver. Since the introduction of recombinant human EPO (rh-EPO) in 1989 through recombinant DNA technology, the therapeutic landscape for anemia has been improved. rh-EPO's market expansion has been substantial, with its application extending across various conditions such as chronic kidney disease, cancer-related anemia, and other disorders. Despite its success, significant concerns remain regarding the stability of EPO, which is critical for preserving its biological activity and ensuring therapeutic efficacy under diverse environmental conditions. Instability issues, including degradation and loss of biological activity, challenge both drug development and treatment outcomes. Factors contributing to EPO instability include temperature fluctuations, light exposure, and interactions with other substances. To overcome these challenges, pharmaceutical research has focused on developing innovative strategies such as stabilizing agents, advanced formulation techniques, and optimized storage conditions. This review article explores the multifaceted aspects of EPO stability, examining the impact of instability on clinical efficacy and drug development. It also provides a comprehensive review of current stabilization strategies, including the use of excipients, lyophilization, and novel delivery systems.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"930-944"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-19DOI: 10.1080/10837450.2024.2414379
Vijayakumari Mahadevan Hari Priya, Anand Ganapathy A, Midhu George Veeran, Shyni Raphael M, Alaganandam Kumaran
Erectile dysfunction (ED), is a common and multidimensional sexual disorder, which comprises changes among any of the processes of the erectile response such as organic, relational, and psychological. However, both endocrine and nonendocrine causes of ED produce substantial health implications including depression and anxiety due to poor sexual performance, eventually affecting man's life eminence. Marginally invasive interventions following ED consist of lifestyle modifications, oral drugs, injections, vacuum erection devices, etc. Nevertheless, these conventional treatment regimens follow certain drawbacks such as efficacy and safety issues, and navigate to the development of novel therapeutic approaches such as nanomedicine for ED management. Nanotechnology-centred drug delivery platforms are being explored to minimize these limitations with better in vitro and in vivo effectiveness. Moreover, nanomedicine and nanocarrier-linked approaches are rapidly developing science in the nanoscale range, which contributes to site-specific delivery in a controlled manner and has generated considerable interest prominent to their potential to enhance bioavailability, decrease side effects, and avoidance of first-pass metabolism. This review provides an overview of recent discoveries regarding various nanocarriers and nano-delivery methods, along with current trends in the clinical aspects of ED. Additionally, strategies for clinical translation have been incorporated.
勃起功能障碍(ED)是一种常见的、多方面的性功能障碍,包括勃起反应过程中的任何变化,如器质性、关系性和心理性。然而,无论是内分泌原因还是非内分泌原因导致的 ED,都会对健康产生重大影响,包括因性功能低下而导致的抑郁和焦虑,最终影响男性的生活质量。治疗 ED 的微创干预措施包括改变生活方式、口服药物、注射、真空勃起装置等。然而,这些传统的治疗方案都存在一定的缺陷,如疗效和安全性问题,这就促使人们开发新型的治疗方法,如用于治疗 ED 的纳米药物。目前正在探索以纳米技术为中心的给药平台,以最大限度地减少这些限制,提高体外和体内疗效。此外,纳米医学和纳米载体连接方法是在纳米尺度范围内快速发展的科学,有助于以可控方式进行特定部位给药,并因其具有提高生物利用度、减少副作用和避免首过代谢的潜力而引起了广泛关注。本综述概述了有关各种纳米载体和纳米给药方法的最新发现,以及 ED 临床方面的当前趋势。此外,还纳入了临床转化策略。
{"title":"Nanotechnology-based drug delivery platforms for erectile dysfunction: addressing efficacy, safety, and bioavailability concerns.","authors":"Vijayakumari Mahadevan Hari Priya, Anand Ganapathy A, Midhu George Veeran, Shyni Raphael M, Alaganandam Kumaran","doi":"10.1080/10837450.2024.2414379","DOIUrl":"10.1080/10837450.2024.2414379","url":null,"abstract":"<p><p>Erectile dysfunction (ED), is a common and multidimensional sexual disorder, which comprises changes among any of the processes of the erectile response such as organic, relational, and psychological. However, both endocrine and nonendocrine causes of ED produce substantial health implications including depression and anxiety due to poor sexual performance, eventually affecting man's life eminence. Marginally invasive interventions following ED consist of lifestyle modifications, oral drugs, injections, vacuum erection devices, etc. Nevertheless, these conventional treatment regimens follow certain drawbacks such as efficacy and safety issues, and navigate to the development of novel therapeutic approaches such as nanomedicine for ED management. Nanotechnology-centred drug delivery platforms are being explored to minimize these limitations with better <i>in vitro</i> and <i>in vivo</i> effectiveness. Moreover, nanomedicine and nanocarrier-linked approaches are rapidly developing science in the nanoscale range, which contributes to site-specific delivery in a controlled manner and has generated considerable interest prominent to their potential to enhance bioavailability, decrease side effects, and avoidance of first-pass metabolism. This review provides an overview of recent discoveries regarding various nanocarriers and nano-delivery methods, along with current trends in the clinical aspects of ED. Additionally, strategies for clinical translation have been incorporated.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"996-1015"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.
{"title":"ROS-responsive glycol chitosan-linked prodrug nanoparticle as a nanoplatform for tumor chemo-photodynamic therapy.","authors":"Jingmou Yu, Mengqi Liu, Chao Zhang, Lizhen Cheng, Changchun Peng, Dengzhao Jiang, Wenbo Liu, Hongguang Jin, Jin Ren","doi":"10.1080/10837450.2024.2411027","DOIUrl":"10.1080/10837450.2024.2411027","url":null,"abstract":"<p><p>Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug <i>via</i> a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc <i>in vitro</i>. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"945-954"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-10DOI: 10.1080/10837450.2024.2413146
Vedant Joshi, Nidhi Singh, Pallab Datta
Microneedles have the potential for minimally invasive drug delivery. However, they are constrained by absence of rapid, scalable fabrication methods to produce intricate arrays and serrations for enhanced adhesion. 3D printing techniques like stereolithography (SLA) are fast, scalable modalities but SLAs require non-degradable and stiff resins. This work attempts to overcome this limitation by utilizing a poly (ethylene glycol diacrylate) (PEGDA, F3) resin and demonstrating its compatibility with a commercial SLA printer. FESEM images showed high printing efficiency of customized bioinks (F3) similar to commercial resins using SLA 3D printer. Mechanical endurance tests of whole MNA showed that MNs array printed from F3 resin (485 ± 5.73 N) required considerably less force than commercial F1 resin (880 ± 32.4 N). Penetration performance of F1 and F3 was found to be 10.8 ± 2.06 N and 0.705 ± 0.03 N. In-vitro degradation study in PBS showed that MNs fabricated from F3 resin exhibited degradation after 7 days, which was not observed with the commercial F1 resin provided by the manufacturer. The histology of porcine skin exhibited formation of triangular pores with pore length of 548 μm and efficient penetration into the deeper dermal layer. In conclusion, PEGDA can be used as for fabricating degradable, serrated solid MNs over commercial resin.
{"title":"Facile fabrication of degradable, serrated polyethylene diacrylate microneedles using stereolithography.","authors":"Vedant Joshi, Nidhi Singh, Pallab Datta","doi":"10.1080/10837450.2024.2413146","DOIUrl":"10.1080/10837450.2024.2413146","url":null,"abstract":"<p><p>Microneedles have the potential for minimally invasive drug delivery. However, they are constrained by absence of rapid, scalable fabrication methods to produce intricate arrays and serrations for enhanced adhesion. 3D printing techniques like stereolithography (SLA) are fast, scalable modalities but SLAs require non-degradable and stiff resins. This work attempts to overcome this limitation by utilizing a poly (ethylene glycol diacrylate) (PEGDA, F3) resin and demonstrating its compatibility with a commercial SLA printer. FESEM images showed high printing efficiency of customized bioinks (F3) similar to commercial resins using SLA 3D printer. Mechanical endurance tests of whole MNA showed that MNs array printed from F3 resin (485 ± 5.73 N) required considerably less force than commercial F1 resin (880 ± 32.4 N). Penetration performance of F1 and F3 was found to be 10.8 ± 2.06 N and 0.705 ± 0.03 N. In-vitro degradation study in PBS showed that MNs fabricated from F3 resin exhibited degradation after 7 days, which was not observed with the commercial F1 resin provided by the manufacturer. The histology of porcine skin exhibited formation of triangular pores with pore length of 548 μm and efficient penetration into the deeper dermal layer. In conclusion, PEGDA can be used as for fabricating degradable, serrated solid MNs over commercial resin.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"976-986"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-10-11DOI: 10.1080/10837450.2024.2409807
Eman A Bseiso, Nermin M Sheta, Khaled M Abdel-Haleem
Drug administration to the central nervous system (CNS) has become a great obstacle because of several biological barriers, such as the blood-brain barrier, therefore, brain targeting insights are a light for scientists to move forward for treating neurogenerative diseases using advanced non-invasive methods. The current demand is to use a potential direct route as the nasal administration to transport drugs into the brain enhancing the BBB permeability and hence, increasing the bioavailability. Interestingly, recent techniques have been implanted in formulating nanocarriers-based therapeutics for targeting and treating ischemic stroke using lipid or polymeric-based materials. Nanoparticulate delivery systems are set as an effective platform for brain targeting as polymeric nanoparticles and polymeric micelles or nanocarriers based on lipids for preventing drug efflux to promote optimal therapeutic medication concentration in the brain-diseased site. In recent years, there has been a notable increase in research publications and ongoing investigations on the utilization of drug-loading nanocarriers for the treatment of diverse CNS diseases. This review comprehensively depicts these dangerous neurological disorders, drug targeting challenges to CNS, and potential contributions as novel intranasal nano-formulations are being used to treat and regulate a variety of neurological diseases.
{"title":"Recent progress in nanoparticulate-based intranasal delivery for treating of different central nervous system diseases.","authors":"Eman A Bseiso, Nermin M Sheta, Khaled M Abdel-Haleem","doi":"10.1080/10837450.2024.2409807","DOIUrl":"10.1080/10837450.2024.2409807","url":null,"abstract":"<p><p>Drug administration to the central nervous system (CNS) has become a great obstacle because of several biological barriers, such as the blood-brain barrier, therefore, brain targeting insights are a light for scientists to move forward for treating neurogenerative diseases using advanced non-invasive methods. The current demand is to use a potential direct route as the nasal administration to transport drugs into the brain enhancing the BBB permeability and hence, increasing the bioavailability. Interestingly, recent techniques have been implanted in formulating nanocarriers-based therapeutics for targeting and treating ischemic stroke using lipid or polymeric-based materials. Nanoparticulate delivery systems are set as an effective platform for brain targeting as polymeric nanoparticles and polymeric micelles or nanocarriers based on lipids for preventing drug efflux to promote optimal therapeutic medication concentration in the brain-diseased site. In recent years, there has been a notable increase in research publications and ongoing investigations on the utilization of drug-loading nanocarriers for the treatment of diverse CNS diseases. This review comprehensively depicts these dangerous neurological disorders, drug targeting challenges to CNS, and potential contributions as novel intranasal nano-formulations are being used to treat and regulate a variety of neurological diseases.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"913-929"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-10-02DOI: 10.1080/10837450.2024.2409812
Shymaa Hatem, Noha H Moftah, Maha H Ragai, Enas El-Maghawry
Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on in-vitro and ex-vivo levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher ex-vivo skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.
{"title":"Development of gallic acid loaded composite nanovesicles for the topical treatment of acne: optimization, characterization, and clinical investigation.","authors":"Shymaa Hatem, Noha H Moftah, Maha H Ragai, Enas El-Maghawry","doi":"10.1080/10837450.2024.2409812","DOIUrl":"10.1080/10837450.2024.2409812","url":null,"abstract":"<p><p>Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on <i>in-vitro</i> and <i>ex-vivo</i> levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher <i>ex-vivo</i> skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"899-911"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-09-30DOI: 10.1080/10837450.2024.2407852
Esraa M Zakaria, Shrouk Fayrouz El-Gamal, Samar Mortada Mahmoud, Hanan M El-Nahas, Hany M El-Bassossy
While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection. Compared to the partial glycemic control achieved with daily oral linagliptin, a weekly subcutaneous injection containing about one-fourth of the oral dose produced superior glycemic control, as evidenced by the 4-week postprandial glucose follow-up and oral glucose tolerance test. This was confirmed by the significant increase in serum insulin in the case of the sustained linagliptin administration. Higher levels of the anti-inflammatory cytokine adiponectin and lower triglyceride levels were observed after sustained linagliptin administration compared with daily oral linagliptin. In addition, sustained linagliptin displayed a significant increase in β-cells' insulin immunoreactivity when compared with daily linagliptin. More reduction in collagen deposition and caspase-3 immunoreactivity in pancreatic tissue were observed in sustained linagliptin compared with oral linagliptin. In conclusion, sustained linagliptin administration provided superior glycemic control, which seems to be mediated by more reduction in pancreatic injury.
{"title":"Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats.","authors":"Esraa M Zakaria, Shrouk Fayrouz El-Gamal, Samar Mortada Mahmoud, Hanan M El-Nahas, Hany M El-Bassossy","doi":"10.1080/10837450.2024.2407852","DOIUrl":"10.1080/10837450.2024.2407852","url":null,"abstract":"<p><p>While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection. Compared to the partial glycemic control achieved with daily oral linagliptin, a weekly subcutaneous injection containing about one-fourth of the oral dose produced superior glycemic control, as evidenced by the 4-week postprandial glucose follow-up and oral glucose tolerance test. This was confirmed by the significant increase in serum insulin in the case of the sustained linagliptin administration. Higher levels of the anti-inflammatory cytokine adiponectin and lower triglyceride levels were observed after sustained linagliptin administration compared with daily oral linagliptin. In addition, sustained linagliptin displayed a significant increase in β-cells' insulin immunoreactivity when compared with daily linagliptin. More reduction in collagen deposition and caspase-3 immunoreactivity in pancreatic tissue were observed in sustained linagliptin compared with oral linagliptin. In conclusion, sustained linagliptin administration provided superior glycemic control, which seems to be mediated by more reduction in pancreatic injury.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"874-885"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1080/10837450.2024.2407854
Rawia M Khalil, Mohamed F Abdelhameed, Sally Abou Taleb, Mohamed A El-Saied, Eman Samy Shalaby
Significance: As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis.
Objective: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption.
Methods: The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis.
Results: Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis.
Conclusion: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.
{"title":"Preparation and characterisation of esculetin-loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis.","authors":"Rawia M Khalil, Mohamed F Abdelhameed, Sally Abou Taleb, Mohamed A El-Saied, Eman Samy Shalaby","doi":"10.1080/10837450.2024.2407854","DOIUrl":"10.1080/10837450.2024.2407854","url":null,"abstract":"<p><strong>Significance: </strong>As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis.</p><p><strong>Objective: </strong>The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption.</p><p><strong>Methods: </strong>The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by <i>in vitro</i> release and <i>in vivo</i> effectiveness on a rat model of UV-induced psoriasis.</p><p><strong>Results: </strong>Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis.</p><p><strong>Conclusion: </strong>As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"886-898"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-22DOI: 10.1080/10837450.2024.2394573
Fatma A Sarhan, Mahmoud E Soliman, Manal Yassin Hamza, Riham I El-Gogary
Fungal infections pose a significant challenge in numerous developing nations and worldwide, necessitating urgent solutions. Oral administration of antifungal medications often leads to severe adverse reactions. Hence, employing topical delivery systems is preferred to ensure efficient dermal delivery of antifungal agents while minimizing side effects. Furthermore, the incorporation of penetration enhancers into nanocarriers loaded with antifungal agents has demonstrated enhanced efficacy in combating mycotic infections. Consequently, ultra-deformable penetration enhancer-containing vesicles (PEVs) were developed to explore this promising approach. In this study, Labrasol® and Transcutol® were used as penetration enhancers in formulating ultra-deformable PEVs containing the antifungal agent Fluconazole (FCZ). The PEVs underwent comprehensive characterization, including measurements of particle size (PS), charge, and entrapment efficiency (EE%). The results revealed that the size of tested PEVs ranged from 100 to 762 nm. All particles exhibited a negative charge, with a minimum zeta potential (ZP) of -38.26 mV, and an intermediate entrapment efficiency (EE%) that reached approximately 40%w/w. Ex-vivo studies demonstrated the ability of PEVs to deliver FCZ to the dermis while minimizing transdermal delivery. The selected formula was tested in-vivo using candidiasis-induced rat model and showed a superiority in its antifungal effect against Candida Albicans compared to the drug control. Stability studies were executed for the selected formula, and revealed good stability shown by the insignificant change in the PS, ZP& EE% over a six-month period.
{"title":"Revolutionizing treatment for topical fungal infections: evaluating penetration-enhancer-containing vesicles as a fluconazole delivery system: <i>Ex-vivo</i> and <i>in-vivo</i> dermal testing.","authors":"Fatma A Sarhan, Mahmoud E Soliman, Manal Yassin Hamza, Riham I El-Gogary","doi":"10.1080/10837450.2024.2394573","DOIUrl":"10.1080/10837450.2024.2394573","url":null,"abstract":"<p><p>Fungal infections pose a significant challenge in numerous developing nations and worldwide, necessitating urgent solutions. Oral administration of antifungal medications often leads to severe adverse reactions. Hence, employing topical delivery systems is preferred to ensure efficient dermal delivery of antifungal agents while minimizing side effects. Furthermore, the incorporation of penetration enhancers into nanocarriers loaded with antifungal agents has demonstrated enhanced efficacy in combating mycotic infections. Consequently, ultra-deformable penetration enhancer-containing vesicles (PEVs) were developed to explore this promising approach. In this study, Labrasol<sup>®</sup> and Transcutol<sup>®</sup> were used as penetration enhancers in formulating ultra-deformable PEVs containing the antifungal agent Fluconazole (FCZ). The PEVs underwent comprehensive characterization, including measurements of particle size (PS), charge, and entrapment efficiency (EE%). The results revealed that the size of tested PEVs ranged from 100 to 762 nm. All particles exhibited a negative charge, with a minimum zeta potential (ZP) of -38.26 mV, and an intermediate entrapment efficiency (EE%) that reached approximately 40%w/w. <i>Ex-vivo</i> studies demonstrated the ability of PEVs to deliver FCZ to the dermis while minimizing transdermal delivery. The selected formula was tested <i>in-vivo</i> using <i>candidiasis</i>-induced rat model and showed a superiority in its antifungal effect against <i>Candida Albicans</i> compared to the drug control. Stability studies were executed for the selected formula, and revealed good stability shown by the insignificant change in the PS, ZP& EE% over a six-month period.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"814-823"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-27DOI: 10.1080/10837450.2024.2393729
George Bebawy, Magda Samir Sokar, Ossama Y Abdallah
Objectives: The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population.
Methods: The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing.
Key findings: The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects.
Conclusion: The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.
{"title":"Buccal lidocaine mucoadhesive patches for pediatrics' teething pain: overcoming possible hazards of oral gels.","authors":"George Bebawy, Magda Samir Sokar, Ossama Y Abdallah","doi":"10.1080/10837450.2024.2393729","DOIUrl":"10.1080/10837450.2024.2393729","url":null,"abstract":"<p><strong>Objectives: </strong>The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population.</p><p><strong>Methods: </strong>The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing.</p><p><strong>Key findings: </strong>The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects.</p><p><strong>Conclusion: </strong>The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"805-813"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}