Pub Date : 2025-12-18DOI: 10.1208/s12249-025-03268-4
Ajay J Khopade, Malay D Shah, Bhushan S Borole, Bharat Patel, Bharat Pateliya, Vinod Burade
This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). In vitro cytotoxicity was assessed in-HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC-MS/MS. PICN demonstrated comparable in vitro cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in Cmax and AUC0-inf across 5-20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.
{"title":"Preclinical Toxicity and Pharmacokinetic Evaluation of Paclitaxel Nanodispersion.","authors":"Ajay J Khopade, Malay D Shah, Bhushan S Borole, Bharat Patel, Bharat Pateliya, Vinod Burade","doi":"10.1208/s12249-025-03268-4","DOIUrl":"https://doi.org/10.1208/s12249-025-03268-4","url":null,"abstract":"<p><p>This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). In vitro cytotoxicity was assessed in-HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC-MS/MS. PICN demonstrated comparable in vitro cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in C<sub>max</sub> and AUC<sub>0-inf</sub> across 5-20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":"60"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772881","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 : 2025-12-17DOI: 10.1208/s12249-025-03287-1
Andrés Felipe Pérez Palacios, Jorge Alexis Medina Parra, Daniel Santiago Córdoba Velasco, Diana Carolina Zona Rubio, Izabel Almeida Alves, Diana Marcela Aragón Novoa
Poor aqueous solubility is a major barrier in drug development, affecting dissolution, absorption, and systemic bioavailability. Nearly 40% of approved drugs and up to 90% of new chemical entities face this limitation, resulting in therapeutic inefficacy and costly clinical development. This study reviewed patents published between 2015 and 2024 that describe technological strategies to enhance drug solubility and bioavailability, aiming to identify innovation trends and their pharmaceutical impact. A structured search was conducted in the Espacenet database using the keywords "bioavailability" and "solubility" under the IPC code A61K. From 98,111 initial results, duplicates, language restrictions, and patents related to cosmetics, nutrition, or veterinary products were excluded, yielding 29 eligible documents. Extracted data included applicant country, therapeutic indication, BCS classification, formulation approach, manufacturing method, and available in vivo pharmacokinetic results. Descriptive analysis was performed using R software. China led patent registrations (55%), followed by the USA (17%). Patent filings increased steadily from 2016-2020, decreased during the COVID-19 pandemic, and recovered after 2021. Most drugs belonged to BCS Class II (76%), reflecting high permeability but poor solubility. The main strategies included particle size reduction, solid dispersions, self-emulsifying drug delivery systems, cyclodextrin inclusion complexes, and advanced crystallization techniques. When reported, pharmacokinetic data showed significant improvements in Cmax and AUC; however, only 58% of patents included in vivo studies. Overall, patents reveal robust innovation aimed at overcoming solubility challenges.
{"title":"New Strategies to Improve Drug Solubility and Its Impact on Bioavailability: A Patent Review (2015-2024).","authors":"Andrés Felipe Pérez Palacios, Jorge Alexis Medina Parra, Daniel Santiago Córdoba Velasco, Diana Carolina Zona Rubio, Izabel Almeida Alves, Diana Marcela Aragón Novoa","doi":"10.1208/s12249-025-03287-1","DOIUrl":"https://doi.org/10.1208/s12249-025-03287-1","url":null,"abstract":"<p><p>Poor aqueous solubility is a major barrier in drug development, affecting dissolution, absorption, and systemic bioavailability. Nearly 40% of approved drugs and up to 90% of new chemical entities face this limitation, resulting in therapeutic inefficacy and costly clinical development. This study reviewed patents published between 2015 and 2024 that describe technological strategies to enhance drug solubility and bioavailability, aiming to identify innovation trends and their pharmaceutical impact. A structured search was conducted in the Espacenet database using the keywords \"bioavailability\" and \"solubility\" under the IPC code A61K. From 98,111 initial results, duplicates, language restrictions, and patents related to cosmetics, nutrition, or veterinary products were excluded, yielding 29 eligible documents. Extracted data included applicant country, therapeutic indication, BCS classification, formulation approach, manufacturing method, and available in vivo pharmacokinetic results. Descriptive analysis was performed using R software. China led patent registrations (55%), followed by the USA (17%). Patent filings increased steadily from 2016-2020, decreased during the COVID-19 pandemic, and recovered after 2021. Most drugs belonged to BCS Class II (76%), reflecting high permeability but poor solubility. The main strategies included particle size reduction, solid dispersions, self-emulsifying drug delivery systems, cyclodextrin inclusion complexes, and advanced crystallization techniques. When reported, pharmacokinetic data showed significant improvements in Cmax and AUC; however, only 58% of patents included in vivo studies. Overall, patents reveal robust innovation aimed at overcoming solubility challenges.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":"57"},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772934","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 : 2025-12-17DOI: 10.1208/s12249-025-03297-z
Komaldeep Kaur, Yogesh A Kulkarni, Sarika Wairkar
Hesperidin, a flavanone, exhibits antioxidant, anti-inflammatory, and anti-amyloidogenic properties, making it a promising candidate for the treatment of Alzheimer's disease. The hesperidin possesses poor solubility, and its oral bioavailability is < 20%. Therefore, hesperidin cochleates (HC) were prepared using the trapping method of calcium ions into preformed liposomes to improve oral bioavailability. The HC formulation was statistically optimized by applying a 3-level factorial design. Optimum cochleates were observed, with an average particle size of 398.9 nm, a zeta potential of -39.1 mV, and an entrapment efficiency of 92.2%, respectively. The in vitro release of hesperidin from cochleates (Batch 15) was 97% in phosphate buffer at pH 7.4 after 24 h. The HC formulation exhibited a 1% release at a gastric pH of 1.2, indicating its stability in the stomach, allowing the formulation to reach the absorption site. In Wistar rats, a comparative pharmacokinetic study was conducted between hesperidin liposomes and HC. Hesperidin concentration was 2.21-fold higher in plasma and 1.2-fold higher in the brain after cochleates administration than in the liposomal formulation and more than 25-fold greater than plain API. Thus, cochleates may be superior oral carriers for hesperidin, improving its oral bioavailability for the treatment of Alzheimer's disease.
{"title":"Improved Oral Bioavailability and Brain Distribution of Hesperidin via Cochleate Formulation: Statistical Optimization and Pharmacokinetic Study.","authors":"Komaldeep Kaur, Yogesh A Kulkarni, Sarika Wairkar","doi":"10.1208/s12249-025-03297-z","DOIUrl":"https://doi.org/10.1208/s12249-025-03297-z","url":null,"abstract":"<p><p>Hesperidin, a flavanone, exhibits antioxidant, anti-inflammatory, and anti-amyloidogenic properties, making it a promising candidate for the treatment of Alzheimer's disease. The hesperidin possesses poor solubility, and its oral bioavailability is < 20%. Therefore, hesperidin cochleates (HC) were prepared using the trapping method of calcium ions into preformed liposomes to improve oral bioavailability. The HC formulation was statistically optimized by applying a 3-level factorial design. Optimum cochleates were observed, with an average particle size of 398.9 nm, a zeta potential of -39.1 mV, and an entrapment efficiency of 92.2%, respectively. The in vitro release of hesperidin from cochleates (Batch 15) was 97% in phosphate buffer at pH 7.4 after 24 h. The HC formulation exhibited a 1% release at a gastric pH of 1.2, indicating its stability in the stomach, allowing the formulation to reach the absorption site. In Wistar rats, a comparative pharmacokinetic study was conducted between hesperidin liposomes and HC. Hesperidin concentration was 2.21-fold higher in plasma and 1.2-fold higher in the brain after cochleates administration than in the liposomal formulation and more than 25-fold greater than plain API. Thus, cochleates may be superior oral carriers for hesperidin, improving its oral bioavailability for the treatment of Alzheimer's disease.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":"59"},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773243","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}
Chemotherapy resistance continues to represent a profound impediment in oncologic therapy, and the co-delivery of chemotherapeutic agents with distinct mechanisms of action offers an effective approach. In the present investigation, we developed Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Sorafenib (SOR), a ferroptosis inducer, and Venetoclax (VTX), an apoptosis inducer for combined cell death. These PLGA(SOR + VTX) NPs were formulated via nanoprecipitation followed by successive coating with polydopamine (PDA) and bovine serum albumin (BSA). PDA was utilized to facilitate BSA linkage while BSA enabled targeting of albondin and secreted protein acidic and rich in cysteine (SPARC) receptors. BSA-PDA-PLGA(SOR + VTX) NPs revealed a spherical morphology with a size of 183.6 ± 6.20 nm, a PDI of 0.108 ± 0.02, and a Z-potential of -23.3 ± 1.03 mV with SOR and VTX ratiometrically (1:1) loaded into the nanoparticles. The nanoparticles exhibited sustained release behaviour and were assessed to be hemocompatible. The cell uptake studies reflected better cytoplasmic internalization, and the formulation resulted in a reduction in the IC50 value by 2.74, 3.40, and 2.90-fold compared to the physical combination of SOR + VTX in MDA-MB-231, A549, and HeLa cell lines, respectively. The apoptosis index of the formulation was 1.42, 1.40 and 1.40-fold higher than that of SOR + VTX in MDA-MB-231, A549 and HeLa, respectively. Moreover, BSA-PDA-PLGA(SOR + VTX) NPs induced a greater generation of reactive oxygen species and mitochondrial membrane potential depolarization. They also demonstrated escalated ferroptosis by depleting glutathione and elevating malondialdehyde levels across all cell lines. Thus, co-delivery of SOR and VTX via BSA-PDA-PLGA NP exhibited synergistic activity in targeting different tumor cells.
{"title":"Exploring the Co-delivery of Sorafenib and Venetoclax to Induce Ferroptosis and Apoptosis Mediated Cancer Cell Death using Surface Modified PLGA Nanoparticles.","authors":"Dhruv Patel, Smriti Bhardwaj, Vivek Yadav, Kaushik Kuche, Pratik Dhake, Sanyog Jain","doi":"10.1208/s12249-025-03304-3","DOIUrl":"https://doi.org/10.1208/s12249-025-03304-3","url":null,"abstract":"<p><p>Chemotherapy resistance continues to represent a profound impediment in oncologic therapy, and the co-delivery of chemotherapeutic agents with distinct mechanisms of action offers an effective approach. In the present investigation, we developed Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Sorafenib (SOR), a ferroptosis inducer, and Venetoclax (VTX), an apoptosis inducer for combined cell death. These PLGA(SOR + VTX) NPs were formulated via nanoprecipitation followed by successive coating with polydopamine (PDA) and bovine serum albumin (BSA). PDA was utilized to facilitate BSA linkage while BSA enabled targeting of albondin and secreted protein acidic and rich in cysteine (SPARC) receptors. BSA-PDA-PLGA(SOR + VTX) NPs revealed a spherical morphology with a size of 183.6 ± 6.20 nm, a PDI of 0.108 ± 0.02, and a Z-potential of -23.3 ± 1.03 mV with SOR and VTX ratiometrically (1:1) loaded into the nanoparticles. The nanoparticles exhibited sustained release behaviour and were assessed to be hemocompatible. The cell uptake studies reflected better cytoplasmic internalization, and the formulation resulted in a reduction in the IC<sub>50</sub> value by 2.74, 3.40, and 2.90-fold compared to the physical combination of SOR + VTX in MDA-MB-231, A549, and HeLa cell lines, respectively. The apoptosis index of the formulation was 1.42, 1.40 and 1.40-fold higher than that of SOR + VTX in MDA-MB-231, A549 and HeLa, respectively. Moreover, BSA-PDA-PLGA(SOR + VTX) NPs induced a greater generation of reactive oxygen species and mitochondrial membrane potential depolarization. They also demonstrated escalated ferroptosis by depleting glutathione and elevating malondialdehyde levels across all cell lines. Thus, co-delivery of SOR and VTX via BSA-PDA-PLGA NP exhibited synergistic activity in targeting different tumor cells.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":"58"},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773177","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 : 2025-12-17DOI: 10.1208/s12249-025-03232-2
Krishna C Telaprolu, Eleftheria Tsakalozou, Priyanka Ghosh, Khondoker Alam, Jeffrey E Grice, Michael S Roberts, Masoud Jamei, Sebastian Polak, James F Clarke
Physiologically based pharmacokinetic (PBPK) modelling can be utilized in dermal drug development and to support regulatory assessments by integrating information related to the active pharmaceutical ingredient (API), drug product, and skin physiology into a mechanistic simulation framework. The purpose of this study was to develop a mechanistic skin absorption model to predict the absorption of lidocaine and prilocaine following topical application of EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) in virtual subjects. The multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA™) model was used to simulate in vitro permeation of both APIs. Changes in formulation pH post application were studied experimentally, and these dynamic changes were captured in the model when simulating finite dose studies using ex vivo human skin. A dermal in vivo PBPK model for the EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) was developed and validated. The model was able to consider the formulation and trial design differences of in vivo studies and adequately simulated the observed data. Further model validation was performed against a manufactured cream with microstructural characteristics that were different compared to the EMLA cream. Through virtual bioequivalence assessments, the in vivo model demonstrated that it may be used to predict the impact of differences in drug product quality attributes on the in vivo performance of a topically applied drug product and inform decisions related to product development.
{"title":"Mechanistic Modelling of Lidocaine and Prilocaine Absorption from EMLA Cream upon Topical Application using Physiologically Based Pharmacokinetic Modelling.","authors":"Krishna C Telaprolu, Eleftheria Tsakalozou, Priyanka Ghosh, Khondoker Alam, Jeffrey E Grice, Michael S Roberts, Masoud Jamei, Sebastian Polak, James F Clarke","doi":"10.1208/s12249-025-03232-2","DOIUrl":"https://doi.org/10.1208/s12249-025-03232-2","url":null,"abstract":"<p><p>Physiologically based pharmacokinetic (PBPK) modelling can be utilized in dermal drug development and to support regulatory assessments by integrating information related to the active pharmaceutical ingredient (API), drug product, and skin physiology into a mechanistic simulation framework. The purpose of this study was to develop a mechanistic skin absorption model to predict the absorption of lidocaine and prilocaine following topical application of EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) in virtual subjects. The multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA™) model was used to simulate in vitro permeation of both APIs. Changes in formulation pH post application were studied experimentally, and these dynamic changes were captured in the model when simulating finite dose studies using ex vivo human skin. A dermal in vivo PBPK model for the EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) was developed and validated. The model was able to consider the formulation and trial design differences of in vivo studies and adequately simulated the observed data. Further model validation was performed against a manufactured cream with microstructural characteristics that were different compared to the EMLA cream. Through virtual bioequivalence assessments, the in vivo model demonstrated that it may be used to predict the impact of differences in drug product quality attributes on the in vivo performance of a topically applied drug product and inform decisions related to product development.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":"56"},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772889","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}
Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.
Area Covered
This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.
Expert Opinion
AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.
{"title":"Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon","authors":"Vaibhavi Srivastava, Pragya Yadav, Abhishek Yadav, Poonam Parashar","doi":"10.1208/s12249-025-03271-9","DOIUrl":"10.1208/s12249-025-03271-9","url":null,"abstract":"<div><h3>Background</h3><p>Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.</p><h3>Area Covered</h3><p>This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.</p><h3>Expert Opinion</h3><p>AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730346","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 : 2025-12-10DOI: 10.1208/s12249-025-03272-8
Sukhada Saraf, Hetal Thakkar, Pranav Shah
Olmesartan Medoxomil (OLM) is a prodrug of an angiotensin II receptor antagonist and a P-glycoprotein (P-gp) substrate that is converted into Olmesartan by esterases, resulting in low oral bioavailability (26%). The aim of the present study was to formulate Olmesartan Medoxomil liposomes by thin film hydration method using Vitamin E TPGS (P gp inhibitor). Initial screening of excipients was conducted using the One Factor At A Time (OFAT) approach, while optimization was performed using Box-Behnken Design (BBD). The drug-to-lipid ratio, the amount of cholesterol, and the surfactant were identified as independent variables, with vesicle size (nm) and entrapment efficiency (%) as dependent variables. Key process parameters were evaluated through OFAT analysis, and the formulation was optimized using BBD. The prepared liposomes were characterized through vesicle size (nm), zeta potential (mV), drug loading (%), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and Gas Chromatography (GC), followed by in vitro dissolution and in vivo pharmacokinetic study in 12 wistar rats. The vesicle size and entrapment efficiency of the optimized formulation were found to be 112.1 nm and 98.88% respectively. In vitro drug release studies were conducted in the USP-II apparatus exhibited a biphasic release pattern compared to the marketed formulation Olmezest®10. In vivo pharmacokinetic studies in wistar rats showed a significant increase in oral bioavailability (3.23 times) of the liposomal formulation of Olmesartan Medoxomil (OLM-LIPO) in comparison to the marketed formulation Olmezest®10.
{"title":"Design of Experiments (DoE) Driven Fabrication of Surface Modified Liposomes of Olmesartan Medoxomil for Improved Oral Bioavailability","authors":"Sukhada Saraf, Hetal Thakkar, Pranav Shah","doi":"10.1208/s12249-025-03272-8","DOIUrl":"10.1208/s12249-025-03272-8","url":null,"abstract":"<div><p>Olmesartan Medoxomil (OLM) is a prodrug of an angiotensin II receptor antagonist and a P-glycoprotein (P-gp) substrate that is converted into Olmesartan by esterases, resulting in low oral bioavailability (26%). The aim of the present study was to formulate Olmesartan Medoxomil liposomes by thin film hydration method using Vitamin E TPGS (P gp inhibitor). Initial screening of excipients was conducted using the One Factor At A Time (OFAT) approach, while optimization was performed using Box-Behnken Design (BBD). The drug-to-lipid ratio, the amount of cholesterol, and the surfactant were identified as independent variables, with vesicle size (nm) and entrapment efficiency (%) as dependent variables. Key process parameters were evaluated through OFAT analysis, and the formulation was optimized using BBD. The prepared liposomes were characterized through vesicle size (nm), zeta potential (mV), drug loading (%), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and Gas Chromatography (GC), followed by in vitro dissolution and in vivo pharmacokinetic study in 12 wistar rats. The vesicle size and entrapment efficiency of the optimized formulation were found to be 112.1 nm and 98.88% respectively. In vitro drug release studies were conducted in the USP-II apparatus exhibited a biphasic release pattern compared to the marketed formulation Olmezest®10. In vivo pharmacokinetic studies in wistar rats showed a significant increase in oral bioavailability (3.23 times) of the liposomal formulation of Olmesartan Medoxomil (OLM-LIPO) in comparison to the marketed formulation Olmezest®10.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720253","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 : 2025-12-10DOI: 10.1208/s12249-025-03238-w
Hong Cheng, Youjie Wang, Zhe Li, Jinzhi Li, Xiao Lin
To improve the functional properties and drying aid role in spray drying of soybean peptide (SP), SP was respectively conjugated with eight saccharides (maltose, lactose, maltodextrin, inulin, α-cyclodextrin (α-CD), β-CD, dextran-20000, and dextran-40000) via wet-heated Maillard reaction, and the efficacy of conjugates in spray-drying of Lycium barbarum extracts rich in low-molecular-weight sugars and organic acids was systematically evaluated. Among the conjugates, SP-α-CD exhibited the highest graft-browning equilibrium index (143.52%) and emulsifying activity index (4.63 m2/g). Through Box-Behnken experimental optimization, the ideal conjugation conditions were identified as: 30 mg/mL SP concentration, 70 °C reaction temperature, and 2.5 h reaction time. When SP-α-CD (10% w/w) co-spray dried with the extract (90%), it could effectively prevent the wall sticking, and the powder yield reached 73.94% (~ 20.74% higher than that achieved by the native SP). The hygroscopicity and softening point (being increased to 69.77 °C) of the powder was improved. X-Ray photoelectron spectroscopy analysis revealed that during spray drying, SP-α-CD tends to distribute on the powder surface, encapsulating the extract components and achieving stronger drying aid and encapsulation effects. Collectively, it is expected to be developed as a spray drying aid for sugar-containing extracts and as a wall material for food and pharmaceutical microencapsulation.
{"title":"Optimized Preparation, Functional Evaluation and Performance in Spray Drying of Soybean Peptide-Saccharide Conjugates Prepared by Wet Heating Maillard Reaction","authors":"Hong Cheng, Youjie Wang, Zhe Li, Jinzhi Li, Xiao Lin","doi":"10.1208/s12249-025-03238-w","DOIUrl":"10.1208/s12249-025-03238-w","url":null,"abstract":"<div><p>To improve the functional properties and drying aid role in spray drying of soybean peptide (SP), SP was respectively conjugated with eight saccharides (maltose, lactose, maltodextrin, inulin, α-cyclodextrin (α-CD), β-CD, dextran-20000, and dextran-40000) via wet-heated Maillard reaction, and the efficacy of conjugates in spray-drying of <i>Lycium barbarum</i> extracts rich in low-molecular-weight sugars and organic acids was systematically evaluated. Among the conjugates, SP-α-CD exhibited the highest graft-browning equilibrium index (143.52%) and emulsifying activity index (4.63 m<sup>2</sup>/g). Through Box-Behnken experimental optimization, the ideal conjugation conditions were identified as: 30 mg/mL SP concentration, 70 °C reaction temperature, and 2.5 h reaction time. When SP-α-CD (10% w/w) co-spray dried with the extract (90%), it could effectively prevent the wall sticking, and the powder yield reached 73.94% (~ 20.74% higher than that achieved by the native SP). The hygroscopicity and softening point (being increased to 69.77 °C) of the powder was improved. X-Ray photoelectron spectroscopy analysis revealed that during spray drying, SP-α-CD tends to distribute on the powder surface, encapsulating the extract components and achieving stronger drying aid and encapsulation effects. Collectively, it is expected to be developed as a spray drying aid for sugar-containing extracts and as a wall material for food and pharmaceutical microencapsulation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720281","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}
Electrospray technology is a process capable of forming monodisperse drug nano/microparticles with enhanced solubility or sustained-release effects. This study aimed to fabricate a sustained-release drug delivery system containing trazodone hydrochloride (TZN-SRDDS) by combining electrospray technology with functional carriers (Soluplus®, Carbopol 940, HPMC K4M, and Lecithin) for solubility improving, drug release prolonging and bioavailability enhancing. The optimized TZN-SRDDS exhibited a spherical morphology, with a particle size of (3.456 ± 0.448) μm, a polydispersity index (PDI) of (0.456 ± 0.024), and a zeta potential of (-17.291 ± 2.351) mV. This system showed a high encapsulation efficiency (97.12 ± 1.82%) and maintained good stability for up to 30 days. In vitro release studies indicated that TZN-SRDDS followed first-order kinetics in pH 1.2 hydrochloric acid solution and the Higuchi model in pH 6.8 phosphate-buffered saline (PBS), with the cumulative release rate increased to (80.81 ± 4.26%); both release profiles exhibited a certain sustained-release effect. Cytotoxicity assays confirmed that TZN-SRDDS was non-toxic at concentrations below 2.6 mg/mL, and the formulation showed a relatively sustained cellular uptake effect. Pharmacokinetic studies in rats showed that the time to reach peak concentration (Tmax) of TZN-SRDDS was extended from 0.25 h to 1 h, its half-life (t1/2) was increased from (1.15 ± 0.17) h to (6.71 ± 0.39) h, resulting in a relative bioavailability of 374.64%. This study achieved the synergistic goals of drug solubilization, sustained-release delivery, and enhanced bioavailability. It provides new technical references for the development of pH-sensitive drug formulations using electrospray technology and also expands the research on the development of sustained-release formulations of trazodone hydrochloride.
{"title":"Sustained-release Drug Delivery System of Trazodone Hydrochloride Based on Electrospray Technology: Preparation, Characterization, In vitro and In vivo Evaluation","authors":"Chengwei Wang, Haiqiao Wang, Michael Adu-Frimpong, Zhihui Zou, Zhou Jin, Peiqi Lu, Zhenrong Liu, Haojie Tian, Ying Xu, Kailun Yang, Jiangnan Yu, Ximing Xu, Yuan Zhu","doi":"10.1208/s12249-025-03291-5","DOIUrl":"10.1208/s12249-025-03291-5","url":null,"abstract":"<div><p>Electrospray technology is a process capable of forming monodisperse drug nano/microparticles with enhanced solubility or sustained-release effects. This study aimed to fabricate a sustained-release drug delivery system containing trazodone hydrochloride (TZN-SRDDS) by combining electrospray technology with functional carriers (Soluplus®, Carbopol 940, HPMC K4M, and Lecithin) for solubility improving, drug release prolonging and bioavailability enhancing. The optimized TZN-SRDDS exhibited a spherical morphology, with a particle size of (3.456 ± 0.448) μm, a polydispersity index (PDI) of (0.456 ± 0.024), and a zeta potential of (-17.291 ± 2.351) mV. This system showed a high encapsulation efficiency (97.12 ± 1.82%) and maintained good stability for up to 30 days. <i>In vitro</i> release studies indicated that TZN-SRDDS followed first-order kinetics in pH 1.2 hydrochloric acid solution and the Higuchi model in pH 6.8 phosphate-buffered saline (PBS), with the cumulative release rate increased to (80.81 ± 4.26%); both release profiles exhibited a certain sustained-release effect. Cytotoxicity assays confirmed that TZN-SRDDS was non-toxic at concentrations below 2.6 mg/mL, and the formulation showed a relatively sustained cellular uptake effect. Pharmacokinetic studies in rats showed that the time to reach peak concentration (T<sub>max</sub>) of TZN-SRDDS was extended from 0.25 h to 1 h, its half-life (t<sub>1/2</sub>) was increased from (1.15 ± 0.17) h to (6.71 ± 0.39) h, resulting in a relative bioavailability of 374.64%. This study achieved the synergistic goals of drug solubilization, sustained-release delivery, and enhanced bioavailability. It provides new technical references for the development of pH-sensitive drug formulations using electrospray technology and also expands the research on the development of sustained-release formulations of trazodone hydrochloride.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712984","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 : 2025-12-05DOI: 10.1208/s12249-025-03286-2
Youfa Xu, Yanting Kuang, Hang Chen, Junyi Zhou, Bingjie Guo, Ruobei Shu, Jiali Wu, Zongguang Tai, Xin Wu
Cabazitaxel (CTX) is primarily used in the clinical treatment of prostate cancer. The clinical CTX injection (Jevtana®) contains the solubilizer Tween 80, which can lead to serious toxic side effects during intravenous injection. This study developed a novel nanodelivery system for encapsulating CTX, eliminating the need for Tween 80 and addressing current clinical challenges associated with CTX use. The nanodelivery system uses the hydrophilic polymer polyvinylpyrrolidone K12 (PVP K12) as a dispersing agent and a small amount of highly biocompatible sodium cholesteryl sulfate (SCS) as a stabilizer, forming a cabazitaxel nanodispersion (CTX-NP) through the water dispersion method. The CTX-NP exhibited a spherical shape, uniform distribution, a particle size of 128.90 ± 0.42 nm, a PDI of 0.14 ± 0.01, a zeta potential of -65.88 ± 1.23 mV, and a drug encapsulation efficiency of 97.58 ± 0.58%. Furthermore, hemolysis, vascular irritation, and maximum tolerated dose (MTD) experiments indicated that CTX-NP has good biocompatibility compared to cabazitaxel-Tween injection (CTX-TW). The pharmacokinetic studies in rats revealed that, compared to CTX-TW, CTX-NP had an extended half-life (T1/2), mean residence time (MRT), and a larger area under the drug concentration–time curve (AUC). In the RM-1 prostate cancer mouse model, compared with CTX-TW, the high-dose CTX-NP group showed better tumor inhibition with an inhibition rate of 79.48%, indicating that CTX-NP could achieve superior anti-tumor effects by increasing the administered dose.
{"title":"Enhanced Efficacy and Safety: Cabazitaxel Nanodispersions as a Novel Therapeutic Platform against Prostate Cancer","authors":"Youfa Xu, Yanting Kuang, Hang Chen, Junyi Zhou, Bingjie Guo, Ruobei Shu, Jiali Wu, Zongguang Tai, Xin Wu","doi":"10.1208/s12249-025-03286-2","DOIUrl":"10.1208/s12249-025-03286-2","url":null,"abstract":"<div><p>Cabazitaxel (CTX) is primarily used in the clinical treatment of prostate cancer. The clinical CTX injection (Jevtana®) contains the solubilizer Tween 80, which can lead to serious toxic side effects during intravenous injection. This study developed a novel nanodelivery system for encapsulating CTX, eliminating the need for Tween 80 and addressing current clinical challenges associated with CTX use. The nanodelivery system uses the hydrophilic polymer polyvinylpyrrolidone K12 (PVP K12) as a dispersing agent and a small amount of highly biocompatible sodium cholesteryl sulfate (SCS) as a stabilizer, forming a cabazitaxel nanodispersion (CTX-NP) through the water dispersion method. The CTX-NP exhibited a spherical shape, uniform distribution, a particle size of 128.90 ± 0.42 nm, a PDI of 0.14 ± 0.01, a zeta potential of -65.88 ± 1.23 mV, and a drug encapsulation efficiency of 97.58 ± 0.58%. Furthermore, hemolysis, vascular irritation, and maximum tolerated dose (MTD) experiments indicated that CTX-NP has good biocompatibility compared to cabazitaxel-Tween injection (CTX-TW). The pharmacokinetic studies in rats revealed that, compared to CTX-TW, CTX-NP had an extended half-life (T<sub>1/2</sub>), mean residence time (MRT), and a larger area under the drug concentration–time curve (AUC). In the RM-1 prostate cancer mouse model, compared with CTX-TW, the high-dose CTX-NP group showed better tumor inhibition with an inhibition rate of 79.48%, indicating that CTX-NP could achieve superior anti-tumor effects by increasing the administered dose.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145675468","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}
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