AAPS PharmSciTech最新文献

{"title":"Cyclodextrin-Based Inclusion Complexes Improve the In Vitro Solubility and Pharmacokinetics of Ivacaftor Following Oral Administration in Mice","authors":"David S. Nakhla,&nbsp;Youssef W. Naguib,&nbsp;Sanjib Saha,&nbsp;Dylan Gao,&nbsp;Nikesh Gupta,&nbsp;Walla Malkawi,&nbsp;Timothy M. Acri,&nbsp;Aliasger K. Salem","doi":"10.1208/s12249-025-03131-6","DOIUrl":"10.1208/s12249-025-03131-6","url":null,"abstract":"<div><p>Cystic fibrosis is a serious life-threatening hereditary disease that occurs due to a mutation in the cystic fibrosis transmembrane conductance regulator gene (<i>CFTR</i>). Ivacaftor (IVA) is a drug that targets the mutated CFTR protein. IVA is highly hydrophobic (log <i>P</i> = 5.6) with poor aqueous solubility (0.05 µg/mL) and is formulated as an amorphous solid dispersion tablet under the brand name Kalydeco^®. The recommended daily dose of Kalydeco^® is twice per day with a high fat meal to aid in IVA’s absorption. In this research, we studied the application of cyclodextrins (CDs) to improve the dissolution of IVA. Phase solubility studies between IVA and four different CDs (α-, β-, γ-, and hydroxypropyl-β-CD [HP-β-CD]) were conducted and a significant improvement in IVA’s aqueous solubility with HP-β-CD was observed. Solid state characterizations confirmed the formation of IVA/HP-β-CD inclusion complexes. <i>In vitro</i> dissolution studies were conducted at pH = 6.8 and showed improvement in IVA’s rate and extent of dissolution with IVA/HP-β-CD (1:2) complexes in comparison to uncomplexed IVA. <i>In vivo</i> pharmacokinetics in mice showed a 2-fold increase in area under the curve (AUC) after the oral administration of the IVA/HP-β-CD complex in comparison to Kalydeco tablets. In addition, HP-β-CD extended the release of IVA from the IVA/HP-β-CD complexes with a longer T_max of 7.05 h compared to 2.96 h with Kalydeco^® tablets. These results demonstrate that CD inclusion complexes of IVA using HP-β-CD can be a successful alternative approach to improving the solubility of IVA while extending its release.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03131-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and In-Vitro Testing of Nebulized Camostat Mesylate Loaded Nanoliposomes for the Treatment of SARS-CoV- 2 Infection","authors":"Rama Kashikar,&nbsp;Arun Kumar Kotha,&nbsp;Rakshya Shrestha,&nbsp;Rudragouda Channappanavar,&nbsp;Mahavir Bhupal Chougule","doi":"10.1208/s12249-025-03099-3","DOIUrl":"10.1208/s12249-025-03099-3","url":null,"abstract":"<div><p>COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (<i>p</i> &lt; 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.</p><h3>Graphical Abstract</h3><p>SARS-CoV- 2</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03099-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Preclinical Testing of a Rapid, High-Volume, Auto-Injector for Subcutaneous Administration with Recombinant Human Hyaluronidase","authors":"Robert J. Connor,&nbsp;Tara Nekoroski,&nbsp;David W. Kang","doi":"10.1208/s12249-025-03116-5","DOIUrl":"10.1208/s12249-025-03116-5","url":null,"abstract":"<div><p>Handheld auto-injectors (AIs) provide a convenient method for subcutaneous (SC) administration of therapeutics in clinical settings or at home via a caregiver or self-administration. However, AIs have been limited to low volumes (&lt; 2 mL), partly due to hyaluronan (HA), a glycosaminoglycan that acts as a barrier to bulk fluid flow in the SC tissue. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that temporarily depolymerizes HA to facilitate the dispersion of SC-administered therapeutics and may enhance the use of AIs capable of delivering high volumes. These studies detail the development and preclinical testing of a novel high-volume AI (HVAI) that successfully delivered 10 mL of a representative macromolecule (immune globulin; Ig) co-administered with rHuPH20 in ≤ 30 s (s) in a miniature pig model. Testing of a surrogate AI informed the development of a novel, clinically-ready prototype HVAI. HVAI injections of Ig co-administered with 2,000 U/mL rHuPH20 improved injection site outcomes (back-leakage, bleb size, swelling, induration) and yielded up to 30% faster injection times compared with injections of Ig alone. In a mock clinical study that replicated clinical settings, the HVAI delivered 10 mL of Ig with 4,000 U/mL rHuPH20 with mean (± standard error of the mean) injection durations of 19.8 s (± 0.5) using a thin-wall 25-gauge (G) needle and 30.0 s (± 1.1) using a standard 25G needle. The data presented here demonstrate the feasibility of the prototype HVAI for rapid, high-volume administration of a concentrated biologic with rHuPH20, and will inform future clinical testing.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03116-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Evaluation of Cyclosporine a Mixed Micelle Eye Drops for Enhanced Ocular Drug Delivery","authors":"Yue Hu,&nbsp;Jiong Wu,&nbsp;Xiaoyan Du,&nbsp;Yan Shen,&nbsp;Daquan Chen,&nbsp;Xiujuan Feng,&nbsp;Dilei Yan","doi":"10.1208/s12249-025-03129-0","DOIUrl":"10.1208/s12249-025-03129-0","url":null,"abstract":"<div><p>Ocular drug delivery is hindered by anatomical and physiological barriers that limit drug bioavailability. Among emerging solutions, mixed micelle systems offer promising potential for enhancing the efficacy of ocular formulations. This study investigates the development and evaluation of a novel cyclosporine A (CsA) micellar eye drop formulation using octylphenol polyethylene glycol ether 40 (OP-40), a surfactant with favorable ocular delivery properties, and polyoxyethylene hydrogenated castor oil 40 (RH-40), a non-ionic surfactant that can enhance the dispersion and stability of the system. OP-40 was optimized through a purification process, and a hybrid micelle system was developed by screening excipients and refining the formulation process. The critical micelle concentration (CMC), crystalline form of CsA, interactions between surfactants and excipients, and the influence of excipients on buffer capacity were systematically examined. The resulting eye drops demonstrated favorable physicochemical characteristics, including pH, osmolality, and stability under both accelerated conditions and long-term storage at room temperature. Furthermore, the formulation exhibited no ocular irritation in rabbit models, confirming its safety. In conclusion, OP-40-based CsA mixed micelle eye drops provide a promising strategy to overcome ocular drug delivery challenges, with significant potential to enhance bioavailability and therapeutic efficacy in ophthalmic applications.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073872","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}

{"title":"Assessment of Emergency Spacers Versus Traditional Spacers, An In-Vitro Model for Aerosol Delivery","authors":"Omar Ahmed Sayed,&nbsp;Mohamed E. A. Abdelrahim,&nbsp;Nabila Ibrahim Laz,&nbsp;Haitham Saeed","doi":"10.1208/s12249-025-03136-1","DOIUrl":"10.1208/s12249-025-03136-1","url":null,"abstract":"<div><p>Spacers, when used with pressurized metered dose inhalers (pMDIs), enhance aerosol drug delivery and address coordination challenges during inhalation. This study aimed to compare the efficacy of emergency spacers with traditional spacers in delivering salbutamol aerosol from pMDIs. The total emitted dose (TED) and particle size distribution of salbutamol were determined using an Andersen MKII cascade impactor. The study evaluated pMDI alone and with various spacers, including traditional antistatic spacers (Able, Tips-Haler, Aerochamber Plus Flow Vu, Atomizer Chamber) and emergency spacers (Plastic juice cup, MDI PLUS, Lite-Air spacer, DispozABLE spacer, and Paper sheet spacer) at a flow rate of 28.3 L/min with inhalation volumes of 2 L and 4 L, representing children (&gt; 6 years) and adults, respectively. The pMDI alone delivered the highest TED, significantly exceeding all pMDI-spacer combinations at both inhalation volumes (<i>P</i> &lt; 0.001–0.033), except for the Aerochamber Plus Flow Vu at 2 L. The Aerochamber Plus Flow Vu achieved significantly higher TED compared to emergency spacers and the Atomizer Chamber (<i>P</i> &lt; 0.001–0.039) and was non-significantly higher than the Able and Tips-Haler spacers. It also delivered the highest fine particle dose (≤ 5 µg) and exhibited the lowest mass median aerodynamic diameter (MMAD) with significant differences across devices. Traditional spacers, particularly the Aerochamber Plus Flow Vu, demonstrated superior performance in TED and aerodynamic particle size distribution. However, emergency spacers remain viable alternatives in urgent situations due to their acceptable delivery efficiency.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03136-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-Engineered Hybridized Polymeric Framework for Chronic Wound Management","authors":"Anbuthiruselvan Solaimuthu,&nbsp;Padmaja Murali,&nbsp;Ane Nishitha Vijayan,&nbsp;Purna Sai Korrapati","doi":"10.1208/s12249-025-03124-5","DOIUrl":"10.1208/s12249-025-03124-5","url":null,"abstract":"<div><p>Chronic wounds, particularly those associated with diabetes, pose a significant challenge in medical care due to their persistent non-healing nature; it is estimated that by 2030, nearly 550 million individuals will be diagnosed with diabetes in the world. This study presents the design and fabrication of a nano-engineered hybridized polymeric framework aimed at enhancing chronic wound management. The designed scaffold is composed of a Polyvinylidene fluoride (PVDF) nanofibrous mat, a Collagen/Polyvinyl Alcohol (PVA) composite loaded with metformin hydrochloride, and polyhydroxybutyrate (PHB) embedded with aceclofenac. The physico-chemical and biochemical characterization of the hybrid scaffold indicated potential efficacy. Electron microscopic studies indicated the porous structure of hybrid polymeric framework (HPF) scaffold which aided significant drug release (metformin and aceclofenac) of 72.2% and 63.9% respectively in 24 h. The hybrid polymeric framework showed swelling of 150–200% to enable drug release along with the efficient exudate absorption that forms the prerequisite for chronic wounds. The HPF scaffold had displayed 93.5% cell viability, 98.7% hemocompatibility, 73.9% <i>in-vitro</i> wound contraction and an improved anti-oxidant activity, that supports the tissue repair in chronic wounds. Thus, the developed hybrid scaffold highlights its potential as an advanced holistic solution for chronic wound management.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073874","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}

{"title":"Nano-Engineered Epigallocatechin Gallate (EGCG) Delivery Systems: Overcoming Bioavailability Barriers to Unlock Clinical Potential in Cancer Therapy","authors":"Mohammad Qutub,&nbsp;Ujban Md Hussain,&nbsp;Amol Tatode,&nbsp;Tanvi Premchandani,&nbsp;Rahmuddin Khan,&nbsp;Milind Umekar,&nbsp;Jayshree Taksande,&nbsp;Priyanka Singanwad","doi":"10.1208/s12249-025-03145-0","DOIUrl":"10.1208/s12249-025-03145-0","url":null,"abstract":"<div><p><i>Epigallocatechin gallate</i> (EGCG), a bioactive polyphenol derived from <i>Camellia sinensis</i>, exhibits multimodal anticancer activity through mechanisms such as apoptosis induction, metastasis suppression, and chemoresistance reversal. Despite its therapeutic promise, clinical application is constrained by rapid metabolism, poor bioavailability, and inconsistent biodistribution. Recent advances in nanotechnology have enabled the development of innovative delivery systems including pH-responsive nanoparticles, lipid-polymer hybrids, and ligand-functionalized carriers that enhance EGCG stability, tumor targeting, and bioavailability by 3- to fivefold in preclinical models. These platforms also facilitate synergistic co-delivery with chemotherapeutics like doxorubicin, amplifying cytotoxicity and overcoming multidrug resistance. Mechanistically, EGCG modulates oncogenic pathways via NF-κB suppression, caspase activation, and MMP-9 downregulation, demonstrating efficacy across diverse cancer types. However, translational challenges persist, such as nanoparticle toxicity, variable tumor accumulation, and insufficient penetration in hypoxic microenvironments. Regulatory hurdles, including the lack of harmonized global standards for herbal medicinal products, further complicate clinical adoption. To bridge these gaps, future research must prioritize scalable cGMP-compliant manufacturing, rigorous preclinical toxicity profiling, and robust clinical trials to validate safety and efficacy. Addressing these issues could position nanoengineered EGCG as a paradigm-shifting therapy in precision oncology, aligning with ESCOP’s mission to integrate evidence-based phytomedicines into conventional cancer care. This review underscores the necessity of interdisciplinary collaboration to standardize phytopreparations, refine regulatory frameworks, and advance biomarker-driven clinical validation, ultimately unlocking the full potential of EGCG in modern therapeutics.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073858","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}

{"title":"Fabrication of 3D Printed Microneedle Patch for the Simultaneous Delivery and Detection of Melatonin from Interstitial Fluid","authors":"Shreya Chauhan,&nbsp;Venkata Vamsi Krishna Venuganti","doi":"10.1208/s12249-025-03139-y","DOIUrl":"10.1208/s12249-025-03139-y","url":null,"abstract":"<div><p>Interstitial fluid (ISF) offers a potential alternative to invasive blood sample collection for biomolecule analysis. Microneedle (MN) patch application can collect ISF in a minimally invasive manner. Polyethylene glycol diacrylate MN patch was fabricated using optimized masked stereolithography-based 3D printing technique. Different 3D printing parameters including ink formula, exposure time, layer thickness, lift speed and distance, printing angle were optimized to fabricate pyramidal MN array. MN patch was characterized for design features, mechanical strength, <i>in vitro, ex vivo</i> and <i>in vivo</i> aspiration of fluid. MN patch aspirated 15 ± 2 µl ISF after application for 10 min in the rat model. Circadian rhythm controlling melatonin hormone was analyzed from ISF. The melatonin concentration ranged from 81 ± 13 to 178 ± 11 pg/ml and 94 ± 20 to 202 ± 6 pg/ml in ISF and serum from light to dark cycle, respectively. Furthermore, two different concentrations of melatonin were loaded in the MN patch during the 3D printing process. The two patches, blank MN patch for collection of ISF for melatonin detection (melatonin aspiration patch) and melatonin loaded patch for delivery (melatonin delivery patch) were simultaneously applied on the rat. Melatonin concentration increased by 4.6 and sixfold in ISF and serum, respectively after application of 20 µg melatonin MN patch, which was determined by blank MN patch application. Taken together, mSLA 3D printing technique can be used to fabricate melatonin loaded MN patch to deliver and collect ISF for melatonin analysis.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073871","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}

{"title":"The Role of Artificial Intelligence in Drug Discovery and Pharmaceutical Development: A Paradigm Shift in the History of Pharmaceutical Industries","authors":"Nithin Vidiyala,&nbsp;Pavani Sunkishala,&nbsp;Prashanth Parupathi,&nbsp;Dinesh Nyavanandi","doi":"10.1208/s12249-025-03134-3","DOIUrl":"10.1208/s12249-025-03134-3","url":null,"abstract":"<div><p>In today’s world, with an increasing patient population, the need for medications is increasing rapidly. However, the current practice of drug development is time-consuming and requires a lot of investment by the pharmaceutical industries. Currently, it takes around 8–10 years and $3 billion of investment to develop a medication. Pharmaceutical industries and regulatory authorities are continuing to adopt new technologies to improve the efficiency of the drug development process. However, over the decades the pharmaceutical industries were not able to accelerate the drug development process. The pandemic (COVID-19) has taught the pharmaceutical industries and regulatory agencies an expensive lesson showing the need for emergency preparedness by accelerating the drug development process. Over the last few years, the pharmaceutical industries have been collaborating with artificial intelligence (AI) companies to develop algorithms and models that can be implemented at various stages of the drug development process to improve efficiency and reduce the developmental timelines significantly. In recent years, AI-screened drug candidates have entered clinical testing in human subjects which shows the interest of pharmaceutical companies and regulatory agencies. End-end integration of AI within the drug development process will benefit the industries for predicting the pharmacokinetic and pharmacodynamic profiles, toxicity, acceleration of clinical trials, study design, virtual monitoring of subjects, optimization of manufacturing process, analyzing and real-time monitoring of product quality, and regulatory preparedness. This review article discusses in detail the role of AI in various avenues of the pharmaceutical drug development process, its limitations, regulatory and future perspectives.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944241","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}

{"title":"Development and Optimization of Stimuli-Responsive Fenugreek/Carrageenan-Co-poly (Methacrylate) Hydrogel Matrices for Controlled Delivery of 5-Fluorouracil","authors":"Muhammad Arslan,&nbsp;Muhammad Umer Ashraf,&nbsp;Ayman M. Al-Qaaneh,&nbsp;Aysha Aslam,&nbsp;Asif Mahmood,&nbsp;Hira Ijaz,&nbsp;Rai Muhammad Sarfraz,&nbsp;Mohamed M. Salem,&nbsp;Milad A. Mezher,&nbsp;Mounir M. Bekhit","doi":"10.1208/s12249-025-03128-1","DOIUrl":"10.1208/s12249-025-03128-1","url":null,"abstract":"<div><p>This study developed novel, stimuli-responsive, biocompatible fenugreek/carrageenanco-poly(methacrylate) hydrogels via free radical polymerization for pH-regulated 5-FU delivery. The hydrogels were evaluated for drug loading (75.2–96.39%), swelling kinetics, sol–gel fraction, electrolyte responsiveness, porosity, and <i>in vitro</i> drug release. Analytical techniques (FTIR, SEM, PXRD, DSC/TGA) confirmed hydrogel formation, drug-excipient compatibility, and thermal stability. FTIR verified cross-linking and 5-FU incorporation, while DSC/TGA and PXRD indicated reduced drug crystallinity and transition to an amorphous form. SEM revealed rough surfaces with porous networks, supporting high drug loading. The hydrogels exhibited pH-responsive swelling, with higher swelling at pH 7.4 (following second-order kinetics) and minimal swelling at pH 1.2. They also responded to monovalent and divalent cations. <i>In vitro</i> release at pH 7.4 showed controlled 5-FU delivery (68.40–96.81%) over 36 h, following non-Fickian diffusion and Higuchi kinetics. Acute oral toxicity studies confirmed biocompatibility and safety. These findings demonstrate that fenugreek/carrageenan-co-poly(methacrylate) hydrogels are promising biocompatible carriers for targeted, controlled 5-FU delivery, offering a safer option for colorectal cancer treatment and other chemotherapy regimens.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944257","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}