AAPS PharmSciTech最新文献

{"title":"Besifloxacin-Loaded Nanostructured Lipid Carrier for Ocular Delivery: Formulation Optimization, In Vitro Characterization, and Safety Assessment","authors":"Mirla Anali Bazan Henostroza,&nbsp;Jéssica Fagionato Masiero,&nbsp;Carolina Falaschi Saponi,&nbsp;Danielle Costa Vargas Redondo,&nbsp;Raimar Löbenberg,&nbsp;Gabriel Lima Barros de Araujo,&nbsp;Nádia Araci Bou-Chacra","doi":"10.1208/s12249-026-03396-5","DOIUrl":"10.1208/s12249-026-03396-5","url":null,"abstract":"<div><p>Conjunctivitis, keratitis, endophthalmitis, and blepharitis are among the most prevalent bacterial eye infections. Topical eye drops are convenient but often exhibit low ocular bioavailability due to anatomical and physiological barriers, which may contribute to subtherapeutic exposure and antimicrobial resistance. Besifloxacin (BFX), a fourth-generation fluoroquinolone approved exclusively for ophthalmic use, has poor aqueous solubility at tear pH and is currently marketed as a suspension requiring frequent instillation. This study aimed to develop and optimize besifloxacin-loaded nanostructured lipid carriers (BFX-NLCs) to improve delivery. BFX-NLCs were prepared by high-pressure homogenization and optimized using response surface methodology, with particle size (Z-average) as the primary response. The optimized formulation exhibited a mean particle size of ~100 nm, a polydispersity index &lt;0.25, and an entrapment efficiency of ~75%. <i>In vitro</i> release in simulated tear fluid showed a sustained release profile, reaching ~65% BFX release at 24 h, best described by the Korsmeyer–Peppas model (diffusion exponent<i> n</i> = 0.86), indicating anomalous (non-Fickian) diffusion. The minimum inhibitory concentrations of BFX-NLC against Staphylococcus aureus ATCC 23235 and Pseudomonas aeruginosa ATCC 9027 were comparable to those of free BFX, demonstrating preservation of antimicrobial activity. BFX-NLCs were non-toxic in the Galleria mellonella larvae model and exhibited suitable viscosity and osmolality for ophthalmic use, as well as physical stability and entrapment efficiency over nine months of storage. These findings support BFX-NLCs as a promising lipid-based platform for topical ocular delivery of besifloxacin, with potential to enhance therapeutic efficacy and reduce dosing frequency in bacterial eye infections.</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":"https://link.springer.com/content/pdf/10.1208/s12249-026-03396-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147642502","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":"Stability Assessment of FDA Approved Varenicline Tartrate Products for Critical Quality Attributes – N-Nitroso Varenicline, Solid Form, and Dissolution","authors":"Mariame A. Hassan,&nbsp;Gereziher Sibhat,&nbsp;Indra K. Reddy,&nbsp;Mansoor A. Khan,&nbsp;Ziyaur Rahman","doi":"10.1208/s12249-026-03358-x","DOIUrl":"10.1208/s12249-026-03358-x","url":null,"abstract":"<div><p>The objectives of the present work were to study the effect of patient-in use and accelerated storage conditions on critical quality attributes (CQAs) of FDA approved varenicline tartrate (VRT) products. Four products (V1, V2, V3 and V4) of VRT were stored at 30 °C/75% RH and 40 °C/75% RH for three and six months, respectively, and tested periodically for nitrite, impurities (N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline), assay, dissolution and solid-state of the drug. Nitrite content decreased while N-nitroso varenicline increased with storage temperature and duration. Initial nitrite value range was 9.3 ± 2.3 to 31.0 ± 9.3 ng/tablet that decreased to 1.7 ± 0.3 to 8.1 ± 5.4 ng/tablet after six months storage at 40 °C/75%. N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline content ranged from 0–31.0 ± 11, 75 ± 9.1 to 5530.0 ± 1.2, and 7.0 ± 0.3 to 1633.2 ± 55.8 ng/tablet after storage, respectively. Polymorphic forms present in V1 and V4 were A and B, respectively, while products V2 and V3 contained amorphous form of the drug. No change in solid state was observed in the products except a decrease in crystallinity of almost 30% after storge. All products completely dissolved &gt; 85% drug in 15 min before storage. V1 and V4 showed no significant change in dissolution while product V2 and V3 showed significant decrease in the dissolution. The dissolved drug was 33.6 ± 0.5 and 34.2 ± 0.7% in 30 min from V2 and V3 after storage, respectively. In summary, tested products showed differential effects of stability conditions on the CQAs and some of the attributes were critically diminished that need further investigation.</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":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03358-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147642714","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":"Functional Reclassification of Lipid-Based Drug Delivery Systems and Advances in Formulation Strategies and Manufacturing Challenges","authors":"Pranal Chhetri","doi":"10.1208/s12249-026-03415-5","DOIUrl":"10.1208/s12249-026-03415-5","url":null,"abstract":"<div><p>Lipid-based drug delivery systems have progressed from a simple empirical solubilization tool towards a highly precise engineered platform, capable of delivering small drug molecules, biologics and nucleic acids. Despite proven achievements reflected through the success of lipid nanoparticles-based mRNA vaccine and siRNA medicines, wider clinical translation across complex diseases still remains limited by a fragmented classification system, inaccurate IVIVC, scale-up complexity and continuously evolving and highly demanding regulatory frameworks. This review re-evaluates lipid systems by providing a functional reclassification system that directly links formulation design with biological performance and scale-up science. Instead of categorising based on simple lipid composition and structural features, lipid-based drug delivery systems are reclassified based on their primary functional roles inside the biological system. Further, this review assesses methods to strengthen IVIVC for Lipid-based drug delivery systems and how quality-by-design and emerging quality-by-digital-design approaches supported by mechanistic modelling, in-process analytical tools and machine learning can be utilised to produce a smart and robust next generation lipid carrier. Lastly, this review also highlights persistent regulatory and transitional challenges, pointing out major gaps related to standardisation, comparability and late-stage failure.</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":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637661","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":"Comprehensive Modalities for Cataract Management: Preventive, Surgical, and Non-Surgical Approaches Using Conventional and Nanotechnology-Based Therapies","authors":"Aya Hussein,&nbsp;Maha El-Kayal,&nbsp;Rehab Nabil Shamma,&nbsp;Asmaa F. Khafaga,&nbsp;Nihal Farid Younes","doi":"10.1208/s12249-026-03384-9","DOIUrl":"10.1208/s12249-026-03384-9","url":null,"abstract":"<div><p>Among ocular diseases, cataract are globally considered the primary cause of blindness. Cataract development is mainly attributed to oxidative stress, which damages epithelial lens proteins and lipids, resulting in clouding or opacification of the normally transparent lens and altering its refractive index. The widespread prevalence of environmental and pathological factors associated with increased cataract risk has heightened interest in innovative therapeutic strategies. Addressing the limitations of current pharmaceutical and surgical interventions is crucial, and the emergence of nanomedicine offers promising opportunities for more precise and effective treatment and prevention strategies compared to conventional methods. Due to their unique properties, nanoparticles have demonstrated significant potential in targeting biological systems and modulating critical physiological processes. This review highlights the potential of various traditional and nanotechnology-based therapeutic agents, including chemical compounds, antioxidants and herbal extracts showing anti-cataract activity both <i>in vitro</i> and <i>in vivo</i>. Furthermore, it explores the benefits and challenges associated with various ocular drug delivery routes for cataract treatment and prevention.</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":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03384-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637634","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":"Harnessing Hybrid Niosomes for Improved Oral Bioavailability of an Anticoagulant: Design, Optimization and In-Vivo Pharmacokinetics and Pharmacodynamics Evaluations","authors":"Remonda Raafat Ragheb,&nbsp;Rodayana Atef,&nbsp;Kareem Abdou,&nbsp;Sadek Ahmed,&nbsp;Ahmed M. Fatouh","doi":"10.1208/s12249-026-03374-x","DOIUrl":"10.1208/s12249-026-03374-x","url":null,"abstract":"<div><p>Venous thromboembolism (VTE) and pulmonary embolism (PE), remains a major global health burden, necessitating prolonged and reliable anticoagulant therapy. Although Apixaban (APX) is a cornerstone oral anticoagulant for VTE management, its therapeutic performance is limited by poor aqueous solubility and low oral bioavailability. To overcome these challenges, this study introduces a hybrid niosomal delivery system designed to enhance the absorption and systemic persistence of APX. The system was engineered by integrating hybrid of surfactants together with cholesterol to form a stable, vesicular matrix. Formulations were prepared via the ethanol injection method and systematically optimized using a 2³ factorial design, assessing the influence of Span 60 concentration (Factor-A), cholesterol: drug ratio (Factor-B), and Tween 80 amount (Factor-C). The optimized formulation achieved a desirability score of 0.738, demonstrating high entrapment efficiency (72.82%), nanoscale particle size (160.05 nm) and a distinctly stable potential (–47.15 mV). TEM imaging confirmed spherical vesicles, and <i>in-vitro</i> release studies revealed a biphasic pattern characterized by an initial burst followed by sustained diffusion. Pharmacodynamics evaluations showed that the optimized formula produced a 1.55-fold increase in cuticle bleeding time (CBT) and a 1.65-fold prolongation in prothrombin time (PT) relative to the APX suspension. Pharmacokinetics assessments further demonstrated enhanced oral bioavailability, evidenced by increased AUC and C_max, along with reduced terminal elimination rate constant (λz) and extended systemic retention. Overall, the developed hybrid niosomes present a promising oral platform for APX delivery, offering improved absorption, and sustained therapeutic action.</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":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03374-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632101","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":"Continuous Manufacturing of Controlled-Release Metoprolol Succinate Tablets by Novel Hot-Melt Fragmentation Technology","authors":"Rajat Radhakrishna Rao,&nbsp;Naitik Jain,&nbsp;Vinay Rao,&nbsp;Indu Bhushan,&nbsp;Srinivas Mutalik","doi":"10.1208/s12249-026-03389-4","DOIUrl":"10.1208/s12249-026-03389-4","url":null,"abstract":"<div><p>A novel metoprolol succinate tablet-in-tablet-in-tablet system was developed using hot-melt granulation combined with twin-screw continuous processing to provide an accurate 24-h sustained release. Tablet-in-tablet-in-tablet system was optimized using Quality by Design, considering key formulation and process parameters such as polymer composition, kneading temperature, screw speed, and feed rate to ensure reproducibility and scalability. The three-layer architecture was tailored to release the drug in a timed sequence, allowing the outer, middle, and core compartments to contribute to a gradual and predictable release profile that closely approached zero-order kinetics. Physicochemical characterization confirmed the stability of metoprolol succinate within the polymeric matrix. Additionally, <i>in vivo</i> studies in rats supported the sustained release behaviour, while accelerated stability testing indicated retention of formulation integrity and dissolution performance for three months. This work describes the development and evaluation of a scalable and robust platform for controlled-release oral dosage forms which could serve as a practical alternative to conventional single-layer or pellet-based systems.</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":"27 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03389-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606743","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":"Polymer Drug Conjugate: A Revolution in Drug Delivery","authors":"Chandan Kumar Singh,&nbsp;Pran Kishore Deb","doi":"10.1208/s12249-026-03411-9","DOIUrl":"10.1208/s12249-026-03411-9","url":null,"abstract":"<div><p>Polymer-drug conjugates (PDCs) represent a remarkable advancement in modern medicine, leveraging the physicochemical properties of polymers to enhance the efficacy and safety of therapeutic agents. This comprehensive review explores the historical evolution, selection criteria, design, and synthesis of PDC, highlighting their transformative impact on drug delivery. The Introduction of biocompatible and biodegradable polymers has been a game-changer, allowing seamless integration with biological systems. We delve into the various polymer selection criteria, focusing on commonly used polymers such as Polyethylene glycol (PEG), Poly Lactic Glycolic Acid (PLGA), and chitosan, and the importance of biocompatibility and biodegradability. The design and synthesis of PDC involve sophisticated chemical and physical conjugation methods, emphasising cleavable and non-cleavable linkers and targeting moieties. We explore the drug-release mechanisms critical for achieving targeted and controlled drug delivery, including pH-sensitive, enzyme-triggered, and redox-sensitive mechanisms. The advantages of PDCs, including improved pharmacokinetics and pharmacodynamics, enhanced targeted delivery, and reduced toxicity, are discussed in detail. Despite their numerous benefits, PDC face challenges, such as stability issues, manufacturing scalability, and immunogenicity. This review addresses these limitations and suggests potential solutions. We also highlight recent advances and innovations in the field, including stimuli-responsive systems, nano PDC, and emerging trends in precision medicine. The applications of PDCs extend beyond cancer therapy, including antimicrobial drug delivery and treatments for cardiovascular and neurodegenerative diseases. Regulatory and commercial aspects are examined, with a focus on FDA-approved PDCs, challenges in clinical translation, and market trends. Future directions for PDCs include integrating Artificial intelligence into conjugate design, developing hybrid systems with other drug-delivery technologies, and advancing sustainable synthesis approaches.</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":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606919","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":"Enhancing Doxorubicin Bioavailability via Dissolving Microneedles: Roles of Drug Loading and Administration Force","authors":"Beibei Yang,&nbsp;Huanhuan Pan,&nbsp;Chunxian Zhou,&nbsp;Jingxin Yang,&nbsp;Wentao Wu,&nbsp;Wenjing Tang,&nbsp;Xin Pan,&nbsp;Chuanbin Wu,&nbsp;Tingting Peng","doi":"10.1208/s12249-026-03412-8","DOIUrl":"10.1208/s12249-026-03412-8","url":null,"abstract":"<div><p>To mitigate the severe adverse effects associated with the systemic administration of doxorubicin (DOX), this study developed a dissolving microneedles (MN) patch loaded with doxorubicin hydrochloride (DOX-MN) for the local treatment of breast cancer. It specifically investigated the influence and underlying mechanisms of drug loading and application force on drug bioavailability. DOX-MN with intact structure and drug enrichment at the needle tips were successfully fabricated using a centrifugal micro-molding technique. Characterization confirmed the excellent mechanical strength and skin insertion capability of the MN, which dissolved rapidly and released the drug within 30 min. <i>In vivo </i>pharmacokinetic studies identified drug loading and application force as critical determinants of bioavailability. A high drug loading potentially created a local supersaturated state, enhancing drug penetration and achieving a relative bioavailability of 65.25%. Increasing the application force to 25 N effectively minimized drug residue on the skin surface, improving bioavailability by approximately 1.5-fold. In a 4T1 tumor-bearing mouse model, DOX-MN administration facilitated efficient drug enrichment and sustained retention at the tumor site, yielding a tumor inhibition rate (90.61%) comparable to intravenous injection. Safety assessments indicated that using a dedicated applicator significantly reduced skin irritation. This study demonstrates that optimizing drug loading and application force enables efficient local DOX delivery via MN, ensuring potent antitumor efficacy while minimizing systemic toxicity, thereby presenting a promising novel strategy for breast cancer therapy.</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":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03412-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606920","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":"Artificial Intelligence-Guided Optimization of Hyaluronic Acid-Coated Liposomal Linagliptin for Targeted Management of Polycystic Ovary Syndrome","authors":"Marwa H. S. Dawoud,&nbsp;Aml H. Zaghloul,&nbsp;Karen S. Zakhari,&nbsp;Mai I. Mahmoud,&nbsp;Zeinab M. Elnagdy,&nbsp;Nyera H. El-Shafei,&nbsp;Mai A. Zaafan","doi":"10.1208/s12249-026-03330-9","DOIUrl":"10.1208/s12249-026-03330-9","url":null,"abstract":"<div><p>Linagliptin, a DPP-4 inhibitor commonly used in the management of diabetes mellitus, has shown potential activity in polycystic ovary syndrome (PCOS). Linagliptin’s therapeutic effectiveness is limited by its poor membrane permeability and low oral bioavailability. This study aimed to formulate hyaluronic acid-coated liposomal linagliptin optimized through I-optimal design and AI-based entrapment efficiency (EE%) prediction. The effects of hyaluronic acid and drug concentrations on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and EE% were systematically evaluated to develop an optimized delivery system for PCOS management. The optimized formulation (O₁) demonstrated a PS of 152.5 nm, PDI of 0.373, ZP of –19.92 mV, and an EE% of 89.43%. The integrated AI-based predictive model achieved 89.8% accuracy, confirming its reliability for rational formulation design. ​<i>In-vitro</i> dissolution studies revealed a sustained drug release over 72 h from O₁, in contrast to complete release within 3 h from unformulated linagliptin. In the PCOS-induced rat model, treatment with both unformulated linagliptin and O₁ significantly improved insulin sensitivity and normalized lipid profiles. Notably, O₁ markedly restored ovarian redox balance through modulation of the Keap1/Nrf2 pathway, indicating a mechanistic basis for the amelioration of PCOS-associated oxidative stress and metabolic dysfunction. Overall, the optimized HA-coated liposomal formulation demonstrated superior therapeutic efficacy and bioavailability compared to unformulated linagliptin, supporting its potential as a targeted repurposed nanocarrier-based therapy for PCOS management, where AI and response surface design are efficient tools for accelerating pharmaceutical formulation development and predicting formulation performance.\u0000</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":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03330-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606851","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":"Albumin Nanoparticle-Based Delivery of Oxaliplatin-Oleic Acid Prodrug for Enhanced Breast Cancer Therapy","authors":"Oly Katari,&nbsp;S. Lokesh,&nbsp;Brojendra Nath Saren,&nbsp;Vivek Yadav,&nbsp;Kaushik Kuche,&nbsp;Sanyog Jain","doi":"10.1208/s12249-026-03353-2","DOIUrl":"10.1208/s12249-026-03353-2","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) remains a therapeutic outlier, with limited targeted options and frequent relapse despite chemotherapy. While platinum therapy can benefit some TNBC cases, including BRCA1/2-mutant tumors, toxicity and limited tumor-selective exposure often restrict its impact. To address these barriers, we applied a lipid-metallodrug prodrug approach and synthesized an oxaliplatin-oleic acid (OXA-OA) conjugate that coupled OXA’s cytotoxicity with OA-associated anticancer activity. The prodrug was encapsulated into genipin-crosslinked albumin nanoparticles (OXA-OA Alb NPs) to improve tumor targeting, yielding a uniform size of 140.52 ± 4.35 nm, a PDI of 0.25 ± 0.05, and an encapsulation efficiency of 84.55 ± 4.49%. Spectrometric analysis confirmed successful OXA-OA conjugation. The nanoparticles demonstrated enhanced cellular uptake and tumor targeting. <i>In vitro</i>, OXA-OA Alb NPs reduced the IC₅₀ to 0.19 ± 0.36 µg/mL (4T1) and 0.20 ± 0.16 µg/mL (MDA-MB-231). This corresponded to 25 to 30-fold higher cytotoxicity than free OXA and &gt; 50-fold than OA. Furthermore, apoptosis indices reached 1.47 (4T1) and 1.42 (MDA-MB-231), which were 4.19- and 4.50-fold higher than OA and 2.43- and 2.53-fold higher than OXA. <i>In vivo</i>, OXA-OA Alb NPs achieved ~ 90% tumor inhibition in a TNBC mouse model, with minimal systemic toxicity, stable liver and kidney function, and reduced organ damage compared with other treatment groups. These findings suggest that OXA-OA Alb NPs offer a promising and safer approach for TNBC, with potential for further exploration in preventing metastasis and recurrence.</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":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606921","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}