AAPS PharmSciTech最新文献

{"title":"Engineering Bilosomal Nanocarriers for Targeted Delivery of Resveratrol: Rational Design, Radiotracking Insights and Cytotoxic Assessment","authors":"Khaled M. Attallah,&nbsp;Shymaa Hatem,&nbsp;Marwa Eid Sayyed","doi":"10.1208/s12249-026-03441-3","DOIUrl":"10.1208/s12249-026-03441-3","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is a major cause of cancer-related death. Resveratrol (RES), despite its promising anti-inflammatory, antioxidant, and anticancer properties, suffers from poor solubility, low bioavailability, and limited tumor accumulation. Accordingly, eight RES-loaded bilosomes were prepared and characterized. Optimization was performed using a desirability study based on the observed colloidal properties. The selected formulation was radiolabeled with iodine-131 and assessed for radiolabeling efficiency and stability. In-vitro cytotoxicity was evaluated against HT- 29 and LS174T CRC cell lines. Biodistribution studies in tumor-bearing mice were also assessed. Bilosomes displayed PS (93.08 to 340.00 nm), negative charges (-27.50 to -51.80 mV), EE% (73.45—96.35%), and a sustained release over a 24-h period. Optimization revealed formulation with PS (163.8 nm), PDI (0.41), EE% (93.80%) and ZP (− 51.8 mV). Radiolabeling efficiency was 93.23 ± 2.15% and was stable for 2 h. In tumor-bearing mice, the tumor uptake of ¹³¹I-RES bilosomes was 4.34-fold compared to ¹³¹I-RES solution, indicating enhanced tumor accumulation and selectivity, likely driven by enhanced permeability and retention-mediated passive targeting. Bilosomes significantly enhanced cytotoxicity, reducing IC₅₀ values ~ fourfold in LS174T and ~ sixfold in HT-29 cells <i>versus</i> free RES. The pharmacokinetic behavior revealed a significantly higher C_max for bilosomes relative to the solution. This study marks the first integration of ¹³¹I-radiotracking with RES-loaded bilosomes, enabling precise measurement of biodistribution and tumor targeting. The approach established a theranostic framework that combined enhanced drug delivery with real-time tracking. Mechanistically, it improved RES accumulation in CRC, highlighting its potential but also underscoring the need for further preclinical research.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03441-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830037","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":"Design, Optimization and Pharmacokinetic Profiling of BCS Class II Drug Loaded Oral Self Nanoemulsifying System","authors":"Ayon Dutta,&nbsp;Swarupananda Mukherjee,&nbsp;Biswajit Basu,&nbsp;Durgesh Ranjan Kar","doi":"10.1208/s12249-026-03439-x","DOIUrl":"10.1208/s12249-026-03439-x","url":null,"abstract":"<div><p>The orally administered self nano emulsifying drug delivery system (SNEDDS), an uniform blend with nano scaled globules, is composed of oil, surfactant and co-surfactant. The aim of the investigation was to develop and optimize Nicardipine loaded liquid SNEDDS via Box Behnken design and characterised based on physicochemical features, DSC and stability profile. Further to achieve sustain drug release, the optimized SNEDDS was compressed as self nano emulsifying tablet (SNET). Furthermore, the <i>in vivo</i> and pharmacokinetic study of the drug loaded SNET (NT) were performed. The NOF indicated droplet size (75.62 nm ± 2.01), self emulsification time (37 s ± 1.01), and 87.6% ± 0.08drug release (at 1 h). The bias was found to be within the range of -0.72 to + 1.19 for stable, almost spherical, amorphous formulation. The sustained release (following Higuchi kinetics) of drug from NT was observed. The mean systolic blood pressure of NT treated rats were found to be significantly reduced (*<i>p</i> &lt; 0.01) to normal range up to 48 h and the plasma NIC concentrations were found to be maintained up to 36 h with enhanced bioavailability in comparison to pure drug suspension. The enhanced NIC exposure of NT (AUC_0-α: 156.1 ± 13.7) compared to pure NIC suspension (AUC_0-α: 89.7 ± 8.1) demonstrated the potentiality of NIC SNET for hypertension treatment.</p><h3>Graphical Abstract</h3><p>Nicardipine hydrochloride loaded oral self-nanoemulsifying system</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829170","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":"PEGylated Flavonoid Aspasomes as a Brain-Targeted Nano-Vesicular Platform for Enhanced Neuroprotection in Stress-Induced Cognitive Dysfunction","authors":"Amal Fathy Aladoly,&nbsp;Maha M. Amin,&nbsp;Heba Nasr Shalaby,&nbsp;Ahmed F. Mohamed,&nbsp;Mohamed Y. Zakaria","doi":"10.1208/s12249-026-03385-8","DOIUrl":"10.1208/s12249-026-03385-8","url":null,"abstract":"<div><p>Luteolin (LUT) is a biologically active flavonoid exhibiting significant therapeutic potential against neurodegenerative disorders such as cognitive impairment. Nonetheless, its clinical application is limited by poor aqueous solubility, extensive first-pass metabolism and diminished permeability across the blood–brain barrier (BBB) and consequently, low oral bioavailability. This study aimed to develop PEGylated LUT nano-vesicular delivery systems to enhance brain delivery and therapeutic efficacy. PEGylated LUT-Aspasomes were prepared via thin-film hydration, using Brij 52 for PEGylation. Sixteen formulations were designed using a 2⁴ full factorial design, varying the weights of Ascorbyl Palmitate (AP), Cholesterol (CH), Brij 52, and Span (Sp) type. The optimized formulation (F14) is composed of 40 mg AP and CH, 10 mg Brij 52, and 50 mg Sp 60 with a desirability value (0.747). F14 demonstrated entrapment efficiency (EE%) (86.24 ± 1.16%), particle size (PS) (188.30 ± 1.50 nm), and zeta potential (ZP) (-25.31 ± 0.84 mV). TEM confirmed spherical, nanosized vesicles with uniform morphology. XRD analysis revealed transformation of LUT from crystalline to amorphous form, supporting successful encapsulation. Drug release and ex-vivo nasal permeation were enhanced 3.4- and fourfold, respectively, compared to free LUT. In-vivo studies in chronic unpredictable stress (CUS) rats revealed that the optimized PEGylated LUT-Aspasomes significantly enhanced neuroprotective effects compared to free LUT. Treated rats exhibited improved spatial memory and a 1.7-fold greater attenuation of depressive-like behavior relative to free LUT. Biochemically, F14 produced 1.15-, 1.23-, and 1.06-fold superior reductions in hippocampal acetylcholinesterase (AChE) activity, serum corticosterone (CORT), and increased brain-derived neurotrophic factor (BDNF) levels, respectively, compared to LUT suspension. Histopathological examination confirmed nearly preserved hippocampal architecture in PEGylated LUT-Aspasome–treated rats. These effects are attributed to LUT encapsulation within PEGylated Aspasomes, which enhanced stability, brain delivery, and neuroprotective efficacy. Thus, PEGylated LUT-Aspasomes are a promising strategy for managing stress-related neurobehavioral disorders.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03385-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829452","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":"Impact of Amino Acid Excipients on icIEF Method Development in Protein Therapeutics: A Formulation-Aware Analytical Framework","authors":"Pragya Manandhar,&nbsp;Nicole Payung,&nbsp;Siddharth Sapa,&nbsp;Matthew Myers,&nbsp;Zaneta Maijorovaite,&nbsp;Haichen Nie","doi":"10.1208/s12249-026-03436-0","DOIUrl":"10.1208/s12249-026-03436-0","url":null,"abstract":"<div><p>Accurate assessment of charge heterogeneity and isoelectric point (pI) is essential for ensuring the quality, stability, and safety of biotherapeutics throughout development and commercialization. Imaged capillary isoelectric focusing (icIEF) is the industry‑standard technique for this purpose, using a stable, linear pH gradient to accurately localize analyte peaks relative to calibrant pI markers. Although amino acids are widely used as formulation excipients for physicochemical stabilization, their potential to interfere with icIEF analyses has not been systematically evaluated. In this study, we investigated the influence of amino acids, with varying pI values and physicochemical properties, on the pH‑gradient linearity, peak focusing, and experimental pI determination of monoclonal antibodies (mAbs). Using a six-pI marker ladder and two representative mAbs (Immunoglobulin-G1: IgG1 and Immunoglobulin-G4: IgG4), our findings demonstrated that amino acids with pI values outside the analyte’s focusing region (e.g., arginine, glutamic acid) can shift peak positions within the capillary window without disrupting calibration linearity, thereby preserving the consistent determination of pI values. In contrast, amino acids with pI values within the focusing region (e.g., glycine, histidine, alanine, leucine) induced localized gradient distortion and generated concentration‑dependent pI shifts. Our case studies highlight conditions under which rational pI marker selection mitigated these effects, as well as a scenario with histidine‑containing IgG4 formulations, in which co‑focusing of IgG4 and histidine could not be simply corrected by calibration adjustments. Based on these findings, we propose a formulation design space that quantitatively relates protein concentration, amino acid excipient levels, and assay dilution requirements to minimize analytical interference. This framework provides practical guidance for integrating formulation strategy to support more reliable icIEF method development to ensure high-quality data throughout the biotherapeutic lifecycle.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829453","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 Evaluation of Tofacitinib Tablets with Comparative Dissolution and Pharmacokinetic Studies in Beagle Dogs","authors":"Deokkyu Lee,&nbsp;Jain Koo,&nbsp;Hyewon Jeon,&nbsp;Jaehyun Cheong,&nbsp;Dongmin Park,&nbsp;Kyung Taek Oh","doi":"10.1208/s12249-026-03444-0","DOIUrl":"10.1208/s12249-026-03444-0","url":null,"abstract":"<div><p>Tofacitinib (Tofa), a Biopharmaceutics Classification System Class III drug, exhibits pH-dependent solubility and a strong tendency to agglomerate, potentially affecting tablet uniformity, <i>in vitro</i> dissolution behavior, and <i>in vivo</i> performance. In this study, a Tofa free base tablet (WT2) prepared by wet granulation was evaluated in Beagle dogs and compared with a marketed reference tablet (RT). <i>In vitro</i> dissolution studies showed comparable drug release between WT2 and RT at pH 1.2 and 4.0, whereas WT2 exhibited slower, though still complete, dissolution at pH 6.8. Despite these differences, pharmacokinetic studies demonstrated comparable systemic exposure under both fasted and fed conditions. The geometric mean ratios and 90% confidence intervals for maximum plasma concentration (C_max) and area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUC_last) met conventional bioequivalence criteria. Food intake slightly delayed absorption but had no significant effect on the extent of exposure. This research shows that differences in dissolution arising from pH-dependent solubility did not meaningfully affect systemic exposure of Tofa free base under the studied conditions.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829542","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":"Formulation Development of Topical Inserts Containing Doxycycline and Doxycycline Combined with Tenofovir Alafenamide and Elvitegravir for the Prevention of Sexually Transmitted Infections","authors":"Vivek Agrahari,&nbsp;M. Melissa Peet,&nbsp;Jasmin Monpara,&nbsp;Rijo John,&nbsp;Sriramakamal Jonnalagadda,&nbsp;Pardeep K. Gupta,&nbsp;Meredith R. Clark,&nbsp;Gustavo F. Doncel","doi":"10.1208/s12249-026-03427-1","DOIUrl":"10.1208/s12249-026-03427-1","url":null,"abstract":"<div><p>Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 mg) and elvitegravir (EVG; 16 mg) to target both bacterial STIs and HIV. Inserts were manufactured using a simple and cost-effective process. Drug loading was within 95–105% of the labeled amount, confirming a robust manufacturing process. <i>In vitro</i>, the inserts disintegrated within 10 min with &gt; 95% drug release within 60 min. The dissolution behavior of DOX inserts showed surface erosion but was affected by medium volume and drug amount. The inserts met key physicochemical targets: hardness (5-8 kg), friability (&lt; 1%), moisture content (&lt; 2%), and osmolality (&lt; 550 mOsm/kg). Based on 6-month storage stability, DOX inserts maintained their physicochemical properties, indicating a shelf life of &gt; 2 years. Preliminary 1-month stability of TED inserts under accelerated conditions showed preservation of their physicochemical properties. These data describe the formulation development and <i>in vitro</i> characterization of topical inserts containing DOX alone or in combination with antiretrovirals (TAF and EVG). Both inserts offer a novel, on-demand topical STI prevention option that supports flexible PrEP/PEP use by both women and men.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03427-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829171","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":"From Digital Design to Dosage Performance: Material-Process-Geometry Interactions in 3D-Printed Oral Tablets","authors":"Aarya Rajendra Menkudale,&nbsp;Prerana V. Poojary,&nbsp;Swohinee Sarkar,&nbsp;Shaila Angela Lewis","doi":"10.1208/s12249-026-03437-z","DOIUrl":"10.1208/s12249-026-03437-z","url":null,"abstract":"<div><p>Additive manufacturing (AM) allows for digital control of the geometry, internal design, and dosage of oral solid dosage forms, thus broadening the horizon of applications. However, the release of drugs from 3D-printed tablets is often explained in terms of geometry alone, without adequate attention to material properties and processing conditions. This review argues that release behavior is the result of material-geometry-process interactions, rather than geometry alone. A critical analysis of the recent literature (2019–2025) on various methods such as fused deposition modeling (FDM), selective laser sintering (SLS), stereolithography/digital light processing (SLA/DLP), semi-solid extrusion (SSE), powder-bed deposition, and inkjet printing reveals the contexts in which geometry can be controlled. Generally, geometry affects release only within material-process stability windows, which are determined by the rheology of polymers, thermal processing, powder sintering, photopolymer crosslink density, or droplet transport. In these contexts, geometry is a secondary control parameter after material state optimization and process development. This review combines the paradigms of Quality by Design (QbD) and Process Analytical Technology (PAT), focusing on real-time monitoring of key process variables and microstructural critical quality attributes to control geometry. The results have implications for regulatory and translational issues, such as inter-printer variability, feedstock qualification, and the absence of geometry-specific bioequivalence guidelines. By viewing geometry-controlled release as an effect of material-geometry-process interactions, this review offers a mechanistic and quality-focused rationale for technology choice, formulation development, and regulatory compliance in pharmaceutical additive manufacturing.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03437-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829454","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":"Understanding the Influence of Molarity, Buffer Capacity, and pH on Product-specific Guidance Dissolution Method for Developing a Discriminatory Dissolution Method for the Development of Mesalamine Products","authors":"Ankit Kumar,&nbsp;Sakshi Kunjir,&nbsp;Prakash Kumar Sirvi,&nbsp;Ayush Rohila,&nbsp;Sadhana Dhyagala,&nbsp;Rajkumar Malayandi","doi":"10.1208/s12249-026-03434-2","DOIUrl":"10.1208/s12249-026-03434-2","url":null,"abstract":"<div><p>Achieving therapeutic intraluminal Mesalamine (MES) concentration at colonic lesion sites is influenced by variable gastrointestinal (GI) pH, buffer capacity (β), fluid volume, viscosity, and transit time. Conventional dissolution tests often overpredict <i>in vivo</i> performance, limiting their relevance for pharmacokinetic prediction. The present study focuses on understanding the impact of pH, molarities, and β on the dissolution behaviour of the MES products and generics. This study evaluates the effect of dissolution media on Prolonged-release granules (PRGs) and Multi-Matrix (MMX®) tablets, and their generics, using product-specific guidance (PSG) protocols across dissolution media and buffer strengths (25, 50, and 160 mM). PRGs showed slower release in low molarity media. It was observed that there was no β effect on the drug release profile in acetate media, where MES remains a poorly soluble zwitterion at pH 4.3. MMX® tablets were sensitive to buffer molarity; 25 mM phosphate buffer caused slower release, revealing differences that were masked under high-molarity Quality Control (QC) media. In 160 mM phosphate buffer, MMX® generics were similar to the reference, but did not meet the f₂ criteria in 25 mM buffer, demonstrating the discriminatory power of low-β media. Overall, molarity, β and pH critically influence MES release, suggesting that different dissolution methods for MES formulations with respect to their discriminatory power should be a valuable tool to mitigate bioequivalence failures in generic development.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829382","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 Application of Machine Learning in the Development of Co-Amorphous Dry Powder Inhalation","authors":"Ziling Zhou,&nbsp;Xian Chen,&nbsp;Yuxin Liu,&nbsp;Rongjiao Zheng,&nbsp;Junxiang Huang,&nbsp;Xin Pan,&nbsp;Chuanbin Wu,&nbsp;Junhuang Jiang","doi":"10.1208/s12249-026-03438-y","DOIUrl":"10.1208/s12249-026-03438-y","url":null,"abstract":"<div><p>Besides improving drug solubility and stability, co-amorphous systems (COAMS) have recently been reported to enhance the pulmonary delivery efficiency of dry powder inhalation (DPI), offering a novel approach to the development of DPI. Conventional drug formulation development utilizes trial-and-error experiments, which require a laborious workload and resources. Moreover, the correlation of forming COAMS to enhanced pulmonary deposition remains underrepresented. Therefore, we proposed applying multiple machine learning (ML) models to the development of co-amorphous DPIs. In this study, we first constructed the database of COAMS through literature mining and then preprocessed the dataset with a molecular representation method. Subsequently, we successfully developed and evaluated the predictive performance of multiple ML models (i.e., logistic regression, random forests, XGBoost, LightGBM, and support vector machines) for forming a co-amorphous system. The five ML models' performance varied, yet all achieved satisfactory predictive accuracy (ACC) of around 0.80 in the testing subset. Specifically, LightGBM exhibited the highest ACC of 0.790 in cross-validation and 0.845 in the testing subset. In addition, SHapley Additive ex Planations (SHAP) analysis revealed that several molecular features (i.e., API_EState_VSA10, Co-former_BCUT2D_MRHI) are critical for models' prediction. More importantly, we conducted experimental validation by using salbutamol sulfate and indomethacin as model drugs to prepare co-amorphous DPIs based on the fine-tuned LightGBM model. The co-amorphous DPIs showed satisfactory aerodynamic performance with fine particle fractions of 41.87%—69.30%. In conclusion, we successfully demonstrated the feasibility of ML for guiding the formation of co-amorphous DPIs, further facilitating the development process in the future.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829162","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":"Mesoporous Silica Nanoparticles for Ocular Drug Delivery: Synthesis, Functionalization, and Safety Insights","authors":"Lajja Patel,&nbsp;Tejal Mehta","doi":"10.1208/s12249-026-03426-2","DOIUrl":"10.1208/s12249-026-03426-2","url":null,"abstract":"<div><p>This review explores mesoporous silica nanoparticles (MSNs) as emerging nano-drug delivery systems for ocular diseases and provides a comprehensive overview of their application in ophthalmic drug delivery, including eye anatomy, ocular barriers, MSNs structural characteristics, synthesis approaches, surface functionalization strategies, drug-loading mechanisms, as well as recent advances in patents and clinical trials. Among all the senses, vision plays a crucial role in everyday life. Ocular disease causes visual impairment and significantly reduces the quality of life, resulting in expensive medical care. Currently used treatments mostly utilize traditional formulations, which are limited by the physiological and anatomical barriers of the eye. Nanotechnologies, particularly MSNs, have emerged as a promising approach to overcome these limitations by enhancing drug loading, targeted drug delivery, and sustained release. An extensive literature review on the synthesis, functionalization, toxicity, safety, and applications of MSNs was conducted using multiple databases, including relevant patents and research studies. The reviewed articles demonstrated that MSNs exhibited improved drug penetration, improved mucoadhesion which extends longer precorneal residence duration, clinical efficacy and acceptable safety profile. Several recent research papers and patents further support the potential of MSNs in treating several ocular disorders effectively. According to the extensive literature survey, MSN-based nanodrug delivery systems provide significant advantages over conventional ocular formulations by overcoming ocular obstacles and enhancing therapeutic effect. Further standardized and clinical research is needed to validate their safety, long-term stability, and clinical effectiveness. Overall, MSNs represent a promising platform with significant potential for ophthalmic drug delivery.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829215","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}