AAPS PharmSciTech最新文献

{"title":"Influence of pH, Buffering Capacity, Ionic Strength, Bile Salts, and Model Drugs on Micellization Behaviour of Salcaprozate Sodium in Physiological Range pH Buffers","authors":"Sideequl Akbar,&nbsp;Anumol Joseph,&nbsp;Adarsh Malgave,&nbsp;Ankit Kumar,&nbsp;Priyambada Bej,&nbsp;Rajkumar Malayandi","doi":"10.1208/s12249-026-03424-4","DOIUrl":"10.1208/s12249-026-03424-4","url":null,"abstract":"<div><p>Salcaprozate sodium (SNAC) is an FDA GRAS-listed permeation enhancer used in oral semaglutide and vitamin B12 formulations. Although its rapid and reversible membrane-perturbing effects are well recognised, it’s <i>in vivo</i> performance is highly variable. Since effective membrane fluidisation requires permeation enhancers to remain as monomers, the critical micelle concentration (CMC) is a key determinant of efficacy. This study investigated the micellization behaviour of SNAC under physiologically relevant conditions. The CMC of SNAC was determined across physiologically relevant pH buffers using complementary techniques, including conductometry, tensiometry, microvolume UV/Visible spectroscopy, and fluorescence spectroscopy. The effects of electrolytes, bile salts, and selected coadministered drugs on SNAC micellization were evaluated. SNAC did not form micelles under gastric conditions due to increased protonation and low solubility. In contrast, SNAC micellized at intestinal pH 6.8 with a CMC of 6.26 ± 0.38 mM. Physiological factors strongly influenced micellization, particularly under intestinal conditions. The presence of electrolytes significantly reduced the CMC to 3.36 ± 0.03 mM, due to reduced electrostatic repulsion and a counter-ion effect. Bile salts showed a biphasic effect, increasing the CMC at low concentrations and promoting mixed micellization at higher concentrations. Coadministered drugs, including aspirin, metformin, nimesulide, ciprofloxacin, and semaglutide, significantly altered SNAC CMC values. Semaglutide showed a non-monotonic effect, decreasing the CMC at low concentrations but increasing it at higher concentrations due to oligomerisation. These findings provide mechanistic insights into SNAC micellization under physiologically relevant conditions and offer a rational basis for optimising SNAC-based oral drug delivery systems.</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":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728006","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":"Efficient Loading of Rabeprazole Sodium via Porous Anion Exchange Resin for Enteric Delivery","authors":"Hongfei Liu,&nbsp;Luyuan Cai,&nbsp;Yutian Dou,&nbsp;Yingshu Feng,&nbsp;Caleb Kesse Firempong,&nbsp;Guoqing Zhang,&nbsp;Haibing He","doi":"10.1208/s12249-026-03413-7","DOIUrl":"10.1208/s12249-026-03413-7","url":null,"abstract":"<div><p>Rabeprazole sodium (RAB), a widely used proton pump inhibitor for treating gastroesophageal reflux disease (GERD), faces limitations in administration to pediatric and dysphagic patients due to the swallowing difficulties posed by conventional oral solid formulations. To overcome these issues, this study developed a pediatric-friendly oral RAB formulation based on a novel anion exchange resin (AER). The synthesized AER exhibited a regular spherical morphology, high porosity, and uniform particle size distribution. RAB was efficiently loaded via ion exchange to form RAB-loaded AER complexes (RAB@AER), achieving a 1.63-fold higher drug loading capacity than that of conventional resins. RAB@AER were subsequently coated with Eudragit L100 using an emulsion-solvent evaporation method, yielding microcapsules consisting of RAB-loaded AER coated by L100 (RAB@AER@L100). <i>In vitro</i> release studies confirmed the enteric protection of the microcapsules, with negligible drug release in acidic medium (pH 1.2) and sustained release under neutral conditions (pH 6.8). The RAB@AER@L100 enteric suspension was developed by blending the microcapsules with suitable excipients, requiring reconstitution with water before oral administration. Pharmacokinetic evaluation in rats revealed that the reconstituted suspension accelerated drug absorption (T_max = 2 h <i>vs.</i> 3 h for commercial capsules) and achieved a higher peak concentration (C_max = 3.19 <i>vs.</i> 2.82 μg/mL), with a comparable area under the plasma concentration–time curve (AUC_0-12 h). This RAB formulation provides an alternative strategy to enhance swallowing safety and dosing convenience in vulnerable patient.</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":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728043","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":"Optimizing Particle Size of pH Modifiers Enhances Dissolution of Weakly Basic Drugs","authors":"Kejia Wu,&nbsp;Yupeng Feng,&nbsp;Zherui Zhang,&nbsp;Junyao Jiao,&nbsp;Weiwei Zhang,&nbsp;Dandan Wei,&nbsp;Haibing He,&nbsp;Yu Zhang,&nbsp;Tian Yin,&nbsp;Zhihong Bao,&nbsp;Yanjiao Wang,&nbsp;Xing Tang","doi":"10.1208/s12249-026-03418-2","DOIUrl":"10.1208/s12249-026-03418-2","url":null,"abstract":"<div><h3> Objective</h3><p> This study aimed to investigate the pH-dependent dissolution of the weakly basic drug carvedilol (BCS Class II) and systematically examine the influence of citric acid concentration and particle size on its release.</p><h3> Methods</h3><p> A series of dissolution studies was conducted in media simulating the gastrointestinal pH range (1.2-7.8), specifically evaluating the effects of citric acid concentration (3% and 9%) and particle size (fine<b> D</b><b>v</b><b>50</b> 44 μm vs. coarse <b>D</b><b>v</b><b>50</b> 608 μm).</p><h3>Results</h3><p> Under acidic conditions (pH 1.2-1.6), carvedilol solubility was high and the effect of citric acid particle size was negligible (&lt;1.3% difference). In the mid-pH range (3.8-6.5), fine citric acid particles rapidly created an acidic microenvironment (pH 3.5±0.2), enhancing carvedilol solubility 2.1-2.8-fold and improving dissolution by 3.1-15.7% compared to coarse particles; increasing the citric acid concentration from 3% to 9% reduced this particle size-dependent variability. At high pH (6.8-7.8), the effect of citric acid weakened, though coarse particles still prolonged acid release.</p><h3> Conclusion</h3><p> While citric acid concentration universally enhanced carvedilol dissolution, the effect of its particle size was pH-dependent, being negligible at low pH but pronounced at higher pH, where larger particles sustained drug release more effectively.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147707808","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 Design of a Hot-melt Extrusion-Based Amorphous Solid Dispersion to Optimize Palatability of Berberine Hydrochloride with In Vitro and In Vivo Evaluation","authors":"Jiayu Zhang,&nbsp;Shengyu Zhang,&nbsp;Chunxue Wang,&nbsp;Binxin Cai,&nbsp;Hongxuan Yang,&nbsp;Kai Zhuang,&nbsp;Nitin Swarnakar,&nbsp;Sandip Tiwari,&nbsp;Feng Zhou,&nbsp;Wenxi Wang,&nbsp;Yang Zhou,&nbsp;Jiantao Zhang","doi":"10.1208/s12249-026-03419-1","DOIUrl":"10.1208/s12249-026-03419-1","url":null,"abstract":"<div><p>Berberine hydrochloride (BH) is a naturally isoquinoline alkaloid extracted from <i>Coptis</i> species. It possesses an extremely intense bitter taste and is classified as a Biopharmaceutics Classification System (BCS) class III drug, exhibiting high aqueous solubility but limited intestinal permeability. Conventional taste-masking polymers, including Kollicoat® Smart Seal and Eudragit® EPO, are predominantly gastric-soluble. While effective in suppressing bitterness, their use may delay or reduce drug release in the intestine, potentially exacerbating the inherently low oral bioavailability of BH. To overcome this limitation, this study employed the enteric polymer Kollicoat® MAE 100–55 to develop an amorphous solid dispersion (ASD) designed to achieve taste masking without compromising intestinal drug release. Following formulation screening, an amorphous solid dispersion of berberine hydrochloride (BH-ASD) was successfully prepared via hot-melt extrusion. Simulated salivary dissolution and bitterness assessments demonstrated pronounced taste-masking performance, which was further enhanced by the inclusion of a minor amount of citric acid. Under non-sink conditions in pH 6.8 phosphate-buffered saline, the BH-ASD exhibited a moderately increased apparent solubility. Consistent with these findings, <i>in vivo</i> pharmacokinetic studies showed a 2.21-fold increase in oral bioavailability relative to crystalline BH. Overall, this study offers a promising formulation strategy to mitigate bitterness and enhance oral bioavailability. More importantly, this HME-based ASD platform presents a viable and scalable approach for the development of patient-centric oral dosage forms of BH.</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":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147707810","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":"Combining of Spray Drying and Dry Granulation to Prepare Orodispersible Tablets: Influence of Spray-Dried Particle Size on Tablet Properties","authors":"Thao Tranová,&nbsp;Jan Loskot,&nbsp;Petr Koukal,&nbsp;Jitka Mužíková","doi":"10.1208/s12249-026-03431-5","DOIUrl":"10.1208/s12249-026-03431-5","url":null,"abstract":"<div><p>The study investigated how the particle size of spray-dried powders containing a model drug and hypromellose phthalate incorporated to granules impacts the powder flow properties, compressibility, and tablet properties. The spray-dried products were obtained at 3 different atomizing gas flow rates and then incorporated into three tabletting materials using dry granulation. The granulation step increased powder bulk and tap density, and decreased Hausner ratio and compressibility index. The particle size of the spray-dried powder influenced the compressibility of granulated tabletting materials and the tensile strength, friability and wetting time of the tablets. The granules with the largest spray-dried particles showed the highest plastic deformation energy, the highest tensile strength and the lowest friability of tablets. Tablets prepared from all granulated powders had a disintegration time below 3 min (European pharmacopeial limit for orodispersible tablets). The tablets also exhibited immediate-release dissolution profiles, and the dissolution rate accelerated with decreasing particle size. Our results imply that gas flow rate during spray drying affects spray-dried particle size and, consequently the properties of granulated powders, the tabletting process and the final tablet quality. We found well-suited mixture composition and processing conditions enabling the preparation of orodispersible tablets with an immediate-release drug dissolution profile.</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":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147707811","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":"Thermo-Sensitive Polymeric Networks for Next-Generation Wound Management: A Review","authors":"Akshay Kumar,&nbsp;Prachee Nirmale,&nbsp;Suresh Babu Kondaveeti,&nbsp;Arpan Kumar Tripathi,&nbsp;Jailani Shiekmydeen,&nbsp;Sagar Nanaso Salunkhe,&nbsp;Gurjeet Singh Thakur,&nbsp;Mohit Kumar","doi":"10.1208/s12249-026-03423-5","DOIUrl":"10.1208/s12249-026-03423-5","url":null,"abstract":"<div><p>Wound healing is a dynamic and highly coordinated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. However, chronic wounds such as diabetic ulcers, burn injuries, and infected wounds often fail to progress through the normal healing cascade due to persistent inflammation, bacterial infection, excessive oxidative stress, and impaired angiogenesis. Conventional wound dressings and topical therapies frequently show limited therapeutic efficacy because of poor adaptability to the wound microenvironment, inadequate drug retention, and uncontrolled drug release. In this context, thermo-sensitive polymeric networks have emerged as promising smart biomaterials for next-generation wound management. These materials exhibit temperature-responsive sol–gel phase transitions, enabling injectable or topical formulations that transform into stable hydrogels at physiological temperature, thereby ensuring conformal wound coverage, improved drug retention, and sustained therapeutic release. Thermo-responsive polymers such as poly(N-isopropylacrylamide), poloxamers, and chitosan-based derivatives have demonstrated significant potential in promoting wound repair through controlled delivery of antimicrobial agents, growth factors, natural bioactive compounds, and nanotherapeutics. Furthermore, the integration of nanomaterials and multifunctional components within thermo-responsive networks can enhance antibacterial activity, reduce inflammation, stimulate angiogenesis, and accelerate tissue regeneration. This review highlights recent advances in thermo-sensitive polymeric networks for wound management, focusing on material design strategies, therapeutic mechanisms, and biomedical applications. Additionally, current challenges, translational perspectives, and future opportunities for developing multifunctional and clinically adaptable thermo-responsive wound dressings are discussed.</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 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687565","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":"TPGS Modified Phospholipid-free and Cholesterol-free Ethosomes Enhance Chemical Stability and Transdermal Permeation Of Retinol","authors":"Fanjun Xu,&nbsp;Meiting Li,&nbsp;Hang Ruan,&nbsp;Teng Guo,&nbsp;Zhi Wang,&nbsp;Nianping Feng,&nbsp;Yongtai Zhang","doi":"10.1208/s12249-026-03417-3","DOIUrl":"10.1208/s12249-026-03417-3","url":null,"abstract":"<div><p>Retinol has emerged as a star ingredient in the cosmetics industry owing to its remarkable skincare efficacy. However, its major limitations—high irritation potential and chemical instability—necessitate further improvement. We developed a liposome primarily composed of glyceryl monooleate and poloxamer (F127). By hybridizing this with a binary alcohol system comprising a 1:1 (v/v) mixture of propylene glycol and dipropylene glycol, an ethosome (ES) capable of efficiently encapsulating retinol was obtained. Retinol-loaded ES (Ret-ES) was further modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS@Ret-ES), thereby optimizing particle size distribution and drug loading capacity. Increasing the binary alcohol concentration from 10 to 30% caused TPGS@Ret-ES hydrated particle size to sharply decrease from 100 to 50 nm, without significant changes in drug loading or encapsulation efficiency. Compared with retinol aqueous solutions, TPGS@Ret-ES substantially reduced degradation rates at room temperature while maintaining excellent particle size stability. Additionally, incorporating antioxidants tocopheryl acetate and Irganox 1010 further improved chemical stability. Notably, TPGS@Ret-ES simultaneously enhanced transdermal drug permeation and skin retention, with no significant irritation observed following repeated application to the same skin site in guinea pigs. In conclusion, ES represents a highly promising topical delivery carrier, and TPGS@Ret-ES shows considerable potential as a novel formulation for retinol.</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 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687572","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":"Can a Lipid-Containing Co-Processed Excipient Overcome Compression Challenges Associated with a Cohesive and Viscoelastic API?","authors":"Ivana Aleksić,&nbsp;Teodora Glišić,&nbsp;Slobodanka Ćirin-Varađan,&nbsp;Jelena Đuriš","doi":"10.1208/s12249-026-03422-6","DOIUrl":"10.1208/s12249-026-03422-6","url":null,"abstract":"<div><p>Although direct compression is the preferred method for manufacturing tablets, it has very limited application due to the poor flowability and compaction properties of most active pharmaceutical ingredients (APIs). Co-processed excipients have emerged as a possible way to overcome these challenges. In the present study, acetaminophen was selected as a model API to evaluate the potential of a novel lipid-containing co-processed excipient to compensate for unfavorable API properties, such as high cohesiveness and viscoelastic properties. Flowability tests and a comprehensive evaluation of tableting properties, including the USP-recommended compression characterization approach and dynamic compaction analysis, were performed. In addition, the potential of this novel co-processed excipient was compared to the commercially available co-processed excipient RetaLac®. The results showed that the novel co-processed excipient has superior flowability in the presence of acetaminophen compared to RetaLac®. The tensile strength of tablets with the lipid-containing co-processed excipient was significantly influenced by acetaminophen content, and an acceptable value (&gt; 1 MPa) was achieved with 30% API, while a slightly higher tensile strength was obtained with RetaLac®. However, a multifold higher network of compression, detachment and ejection stresses in the case of the commercial <i>vs</i>. novel co-processed excipient indicate a much higher ability of the latter to overcome problems associated with the high adhesiveness of the API. Elastic recovery was significantly affected by compression speed, but strain rate sensitivity analysis indicated that not only the compression speed but also dwell time may be important in achieving acceptable mechanical properties of tablets containing viscoelastic API.</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 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687523","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":"DoE-Optimized Chitosan-Coated pH-Sensitive Liposomes for Targeted Nose-to-Brain Delivery of Temozolomide","authors":"Ashish Jain,&nbsp;Harsh P. Nijhawan,&nbsp;Khushwant S. Yadav","doi":"10.1208/s12249-026-03416-4","DOIUrl":"10.1208/s12249-026-03416-4","url":null,"abstract":"<div><p>Glioblastoma is an aggressive brain tumor with limited treatment efficacy due to poor blood–brain barrier (BBB) penetration and intrinsic resistance. Temozolomide (TMZ), the frontline chemotherapeutic, undergoes rapid hydrolysis at physiological pH, with low systemic bioavailability and efflux-mediated clearance. To address this, we developed chitosan-coated pH-sensitive liposomes (SpH-TMZ-CS-LIPO) that were optimized via Box–Behnken design, achieving 223.48 ± 1.93 particle size, 35.72 ± 0.51 zeta potential, and 78.85 ± 2.62% entrapment. The formulation exhibited pH-sensitive release, with cumulative TMZ release of 92–94% at pH 4.5–5.5, following diffusion-controlled kinetics. <i>Ex vivo</i> permeation across goat nasal mucosa at pH 5.5 showed a 1.39-fold increase in TMZ flux compared to Free TMZ, while mucin adsorption studies demonstrated superior mucoadhesion. In U87MG cells, SpH-TMZ-CS-LIPO showed 4.6-fold higher uptake than Free TMZ and markedly enhanced cytotoxicity, reducing viability to 3.92 ± 1.56% (IC₅₀: 0.396 ± 0.105 µg/mL; &gt; 33-fold improvement), reflecting improved intracellular delivery and pH-responsive release. Following intranasal administration in rats, it reached a C_max of 260.82 ± 9.21 µg/mL in the brain and a brain AUC_₀₋∞ of 12,720.42 ± 252.44 µg/mL* h, &gt; 22-fold higher than Free TMZ, with prolonged cerebral residence (MRT_₀₋∞: 36.52 h, t_₁/₂: 24.80 h) and high nose-to-brain targeting (DTI: 17.72; DTE: 177.2%; DTP: 94.3%). These effects reflect pH-sensitive CHEMS-mediated release and CS-induced mucoadhesion, ensuring optimized CNS accumulation with minimal systemic exposure. Overall, SpH-TMZ-CS-LIPO represents a rationally engineered, non-invasive nanocarrier that markedly enhances TMZ delivery, cytotoxicity, and brain-targeting efficiency, offering a promising strategy for glioblastoma therapy.</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 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687526","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":"Recent Advances in Surface-Engineered Polymeric Nanoparticles for Targeted Paclitaxel Delivery in Breast Cancer Therapy","authors":"Mahak Fatima,&nbsp;Fahad AlQahtani,&nbsp;Prashant Kesharwani","doi":"10.1208/s12249-026-03414-6","DOIUrl":"10.1208/s12249-026-03414-6","url":null,"abstract":"<div><p>Breast cancer remains a leading cause of cancer-related mortality worldwide. Paclitaxel (PTX), a first-line chemotherapeutic agent widely used in breast cancer, is widely used due to its potent mechanism of action against rapidly dividing cancer cells. However, its clinical application is significantly hindered by poor solubility, systemic toxicity, and associated adverse effects. Encapsulating PTX in polymeric nanoparticles presents a promising strategy to overcome these limitations by extending drug release, enhancing drug’s bioavailability, and enabling active targeting. This review uniquely focuses on recent advances in surface-functionalized polymeric nanoparticles specifically engineered for targeted delivery of PTX in breast cancer therapy and consolidates their translational relevance and next-generation design considerations. Unlike general reviews on polymeric nanocarriers, this article specifically focuses on ligand-functionalized polymeric nanoparticles designed for active targeting of breast cancer cells, integrating biological rationale, receptor specificity, and translational relevance. Surface-engineered polymeric nanoparticles functionalized with ligands such as folic acid, hyaluronic acid, aptamers, and peptides can specifically target overexpressed receptors on cancer cells, including CD44, HER2, and folate receptors. These ligand-receptor interactions facilitate receptor-mediated endocytosis, enhancing intracellular drug delivery while minimizing systemic toxicity. The review highlights key design considerations, including ligand density, nanoparticle architecture, and multifunctionality of next-generation PTX nanocarriers. The development of PTX-loaded polymeric nanoparticles with surface modifications represents a significant advancement in precision drug delivery for breast cancer, addressing key treatment challenges and paving the way for clinical translation.</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 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147642500","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}