AAPS PharmSciTech最新文献

{"title":"Leveraging Nanoscience and Strategic Delivery for the Expedition of Osteoporosis","authors":"Pramoda G,&nbsp;Rahul K. Verma,&nbsp;Rahul Shukla","doi":"10.1208/s12249-025-03120-9","DOIUrl":"10.1208/s12249-025-03120-9","url":null,"abstract":"<div><p>Osteoporosis is a globally affecting bone disease characterized by reduced bone mineral density, in which women are more insidious to the disease. It accounts for 8.9 million fractures annually, and about 50% of repeated hip fractures cause permanent disabilities. With the knowledge of determinants and pathology, various FDA-approved drugs and therapies are available for the management of the disease, but the challenges associated with those therapies lead to the adoption of nanotechnology in osteoporosis management. The nanosystems developed for the management of osteoporosis are nanogenerators, nanobubbles, microneedles, nanogels, implantable delivery systems, nanoparticles, nanofibrous scaffolds, and nanocements that probably address the current challenges related to the diagnosis and cure. In view of targeted accumulation of the cargo, various moieties assisted the nanocarrier system for selective distribution to bone, and the development of different types of nanotechnology-based delivery systems has been briefed in this review.</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":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925675","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 Characterization of Chitosan Nanoparticles Containing Quercetin-β-Cyclodextrin Inclusion Complex for Improved Solubility, Brain Targeting, and Neuroprotective Potential Against Epilepsy","authors":"Priyabrata Pradhan,&nbsp;Vineet Kumar Rai,&nbsp;Jitu Halder,&nbsp;Durgamadhab Kar,&nbsp;Shakti Ketan Prusty,&nbsp;Saroj Kumar Rout,&nbsp;Salim Manoharadas,&nbsp;Subramanian Palanisamy,&nbsp;Priyanka Dash,&nbsp;Chandan Das,&nbsp;Biswakanth Kar,&nbsp;Goutam Ghosh,&nbsp;Goutam Rath","doi":"10.1208/s12249-025-03119-2","DOIUrl":"10.1208/s12249-025-03119-2","url":null,"abstract":"<div><p>The present study focuses on developing and optimising chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex (QNPs) using the nanoprecipitation method to enhance quercetin's solubility, stability, and bioavailability. A comprehensive optimization study revealed that Batch B6, which utilized ethanol as the solvent, poloxamer 188 as the stabilizer, and chitosan at a concentration of 0.2% (w/v), exhibits optimal characteristics required for providing a stable colloidal system. The prepared nanoparticles were characterized for their physicochemical properties using FTIR, DSC, X-ray Diffraction, and SEM, which confirmed the successful inclusion of quercetin within the β-cyclodextrin complex and the reduction in crystallinity. <i>In-vitro</i> drug release studies demonstrated a controlled release profile for QNPs compared to free quercetin and the inclusion complex. Pharmacokinetic evaluation in mice via oral administration revealed a significant enhancement in systemic circulation and brain uptake, with QNPs showing a peak plasma concentration of 6.5 µg/mL at 2 h and a brain concentration of 3.5 µg/g at 4 h, indicating improved bioavailability and prolonged retention. In the Pentylenetetrazole and Kainic acid-induced epilepsy mice model, QNP significantly reduced seizure duration, frequency of seizures, and severity scores favoured the QNP formulation over free quercetin. QNPs also exhibited a significant neuroprotective effect by enhancing antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione reductase in brain tissue. Furthermore, Na⁺/K⁺-ATPase activity was significantly preserved in QNP-treated groups, indicating membrane stability and reduced neuronal excitability. These findings suggest that QNPs offer a promising strategy for enhancing quercetin's therapeutic efficacy in neurological disorders such as epilepsy.</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":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913838","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":"Design, Development, and Characterization of High Drug-Loaded Drug-Drug-Polymer Ternary Amorphous Solid Dispersions","authors":"Sagar Kumar Paul,&nbsp;Dunesh Kumari,&nbsp;Joel Destino,&nbsp;Harsh Chauhan","doi":"10.1208/s12249-025-03123-6","DOIUrl":"10.1208/s12249-025-03123-6","url":null,"abstract":"<div><p>Ternary amorphous solid dispersions (TASD) are a three-component system that incorporates at least one drug in an amorphous form, offering potential advantages over conventional binary amorphous solid dispersions (ASD). This study aimed to design, characterize, and evaluate a stable and soluble high drug-loaded TASD combining two poorly water-soluble drugs, curcumin (CUR) and resveratrol (RES), with a hydrophilic polymer. Polymer screening studies, including miscibility, crystallization tendency, Flory–Huggins interaction parameter, and solubility parameter, were complemented by advanced techniques such as crystallization kinetics and molecular interaction analysis to assess drug-polymer interactions and amorphous stability. After selecting the optimal polymer, TASDs were prepared by rotary evaporation. Pure drugs, physical mixtures, binary, and ternary ASDs were characterized using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy, and Raman spectroscopy. <i>In-vitro</i> dissolution under non-sink conditions was performed using a USP-II apparatus, and centrifuged samples were analyzed by UV–Vis spectroscopy. Long-term physical stability was assessed over 12 months at room temperature. Eudragit EPO was identified as the optimal polymer among EPO, HPMCAS, and S100. The resulting high drug-loaded (50% w/w) TASD was amorphous, exhibiting a single glass transition temperature (Tg) with strong drug-polymer interactions. In dissolution studies, the 50% drug-loaded TASD showed a ~ 197-fold and ~ fourfold increase in dissolved CUR and RES, respectively, compared to the crystalline drugs in the physical mixture after 1 h in acidic condition. Despite a lower RES release, it was still twice the release from binary ASDs. The TASD formulation remained physically amorphous for 12 months at room temperature storage.</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":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913784","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":"Ethyl-Cellulose Nanosponges for Topical Delivery of Simvastatin with Preferential Skin Retention for Wound Healing in a Full-Thickness Wound Rat Model","authors":"Samar Aboelazayem,&nbsp;Maha Nasra,&nbsp;Heba Ebada,&nbsp;Ossama Abdallah","doi":"10.1208/s12249-025-03114-7","DOIUrl":"10.1208/s12249-025-03114-7","url":null,"abstract":"<div><p>Novel topical nanosponges were implemented to improve the skin availability of simvastatin (SV) for treating full-thickness wounds while controlling the scarring process. SV exhibits great potential in treating various skin diseases owing to its antibacterial, antioxidant, anti-inflammatory, and immunomodulatory properties. However, its poor oral bioavailability and systemic side effects have hindered its clinical application in dermatology. For the first time, nanosponges were utilized to target injured skin, creating an SV reservoir within the wound bed to enhance therapeutic efficacy while minimizing adverse effects. Herein, SV-loaded ethyl-cellulose nanosponges (SV-NS) were prepared using the emulsion solvent evaporation technique, optimizing organic solvents, SV concentration, and stabilizer concentration. The selected SV-NS (20 mg SV) exhibited nanoporous particles (786.2 ± 50 nm), a specific surface area of 10.3 m²/g, and a total pore volume of 0.016 cm³/g, offering sustained release and enhanced skin retention capacity. <i>In vivo</i> studies on full-thickness rat wounds confirmed that topical SV-NS (5 mg SV, applied every 5 days) significantly accelerated wound closure (<i>P</i> &lt; 0.0001), achieving 76.23 ± 3.20% closure by day 8, a 47% improvement over free SV. Consequently, SV-NS facilitated wound closure exceeding 90% by day 11, whereas free SV required 16 days to attain a comparable level, representing a 31.2% faster healing rate. Histological analysis further revealed that SV-NS promoted optimal epidermal layer formation and well-organized collagen deposition, with collagen expression significantly (<i>P</i> &lt; 0.0001) reaching 59.85 ± 3.17% by day 16. Conclusively, SV-NS enhances SV’s dermal availability, improving wound healing and minimizing side effects, demonstrating a promising approach for wound restoration.</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":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03114-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913783","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":"Application of a Two-Phase Experiment Design and Optimization Method to Formulate Ciprofloxacin-Loaded Bovine Serum Albumin Nanoparticles with High-Entrapment Efficiency for Targeting Urinary Tract Infections","authors":"Sofía V. Sánchez,&nbsp;Erlen Cruz Jorge,&nbsp;Nicolás Navarro M.,&nbsp;María José González,&nbsp;Ricardo Vásquez,&nbsp;Felipe Del Canto,&nbsp;Paola Scavone,&nbsp;Eva C. Arrúa,&nbsp;Javier O. Morales","doi":"10.1208/s12249-025-03115-6","DOIUrl":"10.1208/s12249-025-03115-6","url":null,"abstract":"<div><p>Urinary tract infections (UTIs), predominantly caused by uropathogenic <i>Escherichia coli</i> (UPEC), pose a global health concern due to rising antibiotic resistance and biofilm formation. Albumin nanoparticles (NPs) offer a promising strategy for UTI treatment, with site-specific selectivity, improved bioavailability, and sustained drug release. This study focused on developing an optimized method for formulating ciprofloxacin-loaded albumin nanoparticles (CPF-loaded BSA NPs) to treat UPEC and its biofilms effectively. A desolvation method was used to synthesize the nanoparticles, and a two-phase experimental design was used for optimization. Evaluation parameters included size, polydispersity index, zeta potential, morphology, encapsulation efficiency, drug release, storage stability, cytotoxicity, and effectiveness against UPEC. The optimized CPF-loaded BSA NPs exhibited desirable characteristics such as small particle size (123 nm), low polydispersity index (0.178), optimum zeta potential (-31.8), and high encapsulation efficiency (&gt; 80%). They also exhibited low cytotoxicity, high stability, and sustained drug release, making them an ideal drug delivery system. Critically, they demonstrated effectiveness against UPEC and its biofilm. This study suggests that the optimized CPF-loaded BSA NPs, synthesized using our optimized desolvation technique, hold the potential for effectively treating UTIs caused by UPEC.</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":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900666","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 Intracellular Uptake of Ivermectin through Liposomal Encapsulation","authors":"Meryem Kocas,&nbsp;Fumiyoshi Yamashita,&nbsp;Tansel Comoglu,&nbsp;Qiyue Zhang","doi":"10.1208/s12249-025-03113-8","DOIUrl":"10.1208/s12249-025-03113-8","url":null,"abstract":"<div><p>Ivermectin (IVM), an antiparasitic drug approved by the Food and Drug Administration (FDA), is widely used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies. Additionally, IVM has shown potential as a potent inhibitor of certain RNA viruses, such as SARS-CoV-2. However, IVM is highly hydrophobic, essentially insoluble in water, which limits its bioavailability and therapeutic effectiveness. The use of liposomes as drug carriers offers several advantages, including enhanced solubility for lipophilic drugs, passive targeting of immune system cells, sustained release, and improved tissue penetration. To address the limitations of IVM, including its poor solubility and bioavailability, liposomal formulations were developed using a combination of soyphosphatidylcholine (SPC), dioleylphosphatidylcholine (DOPC), cholesterol (Ch), and diethylphosphate (DCP) in two distinct molar ratios (1.85:1:0.15 and 7:2:1) via the ethanol injection method. The physicochemical properties of the placebo and IVM-loaded liposomes were extensively characterized in our earlier study, including the particle size, polydispersity index, and zeta potential. The present work adds a deeper level of investigation into how to effect cellular uptake and cytotoxicity <i>in vitro</i> of both free IVM and IVM-loaded liposomes in Vero E6 cells. The half-maximal cytotoxic concentrations (CC₅₀) for free IVM and IVM-loaded liposomes were 10 μM and &gt; 110 μM, respectively and the cellular uptake of IVM-loaded liposomes ranged from 13 to 60%, whereas free IVM showed a significantly lower uptake of only 2%. These results demonstrate that liposomal encapsulation effectively enhances IVM’s cellular uptake while reducing its cytotoxicity, thus offering a promising strategy for improving the effectiveness of IVM.</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":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03113-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900665","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":"Solubilising and Aerosolising Cannabidiol Using Methyl β-Cyclodextrin and Human Serum Albumin","authors":"Waiting Tai,&nbsp;Dipesh Khanal,&nbsp;Jonathon Carl Arnold,&nbsp;Hak-Kim Chan,&nbsp;Philip Chi Lip Kwok","doi":"10.1208/s12249-025-03121-8","DOIUrl":"10.1208/s12249-025-03121-8","url":null,"abstract":"<div><p>Pulmonary delivery can deliver cannabidiol (CBD) with high bioavailability and fast onset of action. One formulation obstacle is the low aqueous solubility of CBD, so solubilsers are necessary. This study aimed to develop inhalable CBD powders using excipients that help dissolving CBD. The solubilisation effects of human serum albumin (HSA), β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and methyl-β-cyclodextrin (mbCD) were investigated with phase solubility test. MbCD showed the highest CBD solubilisation ability at all tested concentrations, followed by HSA. Therefore, mbCD and HSA were co-spray freeze dried with CBD to obtain CBD + mbCD and CBD + HSA powders, respectively. Both powders were amorphous, had &lt; 3% residual solvent, and contained CBD in complexes. CBD + mbCD maintained its amorphicity at &lt; 70% relative humidity. On the other hand, CBD + HSA resisted recrystallisation even at 90% relative humidity. However, although both formulations emitted about 90% of CBD, CBD + HSA was less dispersible than CBD + mbCD (fine particle fraction &lt; 5 µm: 30.2 ± 1.0% <i>vs</i> 53.5 ± 1.5%). The higher level of CBD solubility enhancement and better aerosol performance from mbCD indicated that it was an effective excipient to deliver CBD and potentially other cannabinoids in the future.</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":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03121-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892717","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":"Predicting and Confirming Bioequivalence of Alpelisib Oral Granules and Tablets for Patients With PIK3CA-Related Disorders","authors":"Elise Burmeister Getz,&nbsp;Séverine Niglis,&nbsp;Athanasia Papadimitriou,&nbsp;Marina Statelova,&nbsp;Xiaojun Ren,&nbsp;Keroles Nakhla,&nbsp;Sherif Sharaby,&nbsp;Muzammil Tariq,&nbsp;Luca Garbuio,&nbsp;Sumerah Bakhsh","doi":"10.1208/s12249-025-03109-4","DOIUrl":"10.1208/s12249-025-03109-4","url":null,"abstract":"<div><p>Alpelisib, an oral α-specific phosphoinositide 3-kinase (<i>PI3K</i>) inhibitor, has been shown to be safe and effective for some patients with gain-of-function mutation in the <i>PIK3CA</i> oncogene. Alpelisib has received US FDA accelerated approval as Vijoice® film-coated tablets to treat severe <i>PIK3CA</i>-Related Overgrowth Spectrum (PROS). PROS typically displays clinical manifestations in the first year of patient life. Therefore, oral granules were developed as an age-appropriate pediatric dosage form. Bioequivalence between alpelisib granules and tablet and the effect of food on granules pharmacokinetics were assessed in a single-center, randomized, three-treatment, six-sequence, three-period, crossover study among 60 healthy adults. Participants were randomly assigned to receive a single 50-mg alpelisib dose as: <i>(i)</i> tablet following a meal, <i>(ii)</i> granules following a meal, and <i>(iii)</i> granules while fasting. Statistical analysis of non-compartmental pharmacokinetic parameters demonstrated bioequivalence between the 50-mg alpelisib granules and tablet forms when administered with food: estimated geometric mean ratios (90% confidence interval) for granules-versus-tablet area under the curve (AUC) from time zero to infinity (AUC_inf), to the last measurable concentration (AUC_last) and maximum observed concentration (C_max) were 0.984 (0.952, 1.02), 0.980 (0.946, 1.02), and 0.947 (0.891, 1.01), respectively. No clinically relevant food effect on 50-mg alpelisib granules pharmacokinetics was observed. These results were accurately predicted using physiologically based biopharmaceutical modeling. Alpelisib granules provide a bioequivalent alternative to tablets for patients prescribed a 50-mg dose and have difficulty swallowing tablets, an important consideration for convenience and compliance of this standard-of-care chronic therapy for patients with PROS. This study was registered in ClinicalTrials.gov on January 4, 2022 (NCT05195892).</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":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03109-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892716","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":"Functionalized Niosomes for Co-Delivery of Curcumin and Imatinib Mesylate to Treat Breast Cancer: In Vitro and In Vivo Investigations","authors":"Priyadarshi Aparajay,&nbsp;Harishkumar Madhyastha,&nbsp;Mohammad A. Altamimi,&nbsp;Abhimanyu Dev,&nbsp;Afzal Hussain,&nbsp;Shuvadip Bhowmik","doi":"10.1208/s12249-025-03102-x","DOIUrl":"10.1208/s12249-025-03102-x","url":null,"abstract":"<div><p>Breast cancer is notable for its aggressive mutations, high resistance, and delayed diagnosis. Traditional treatments often cause severe side effects, highlighting the need for targeted therapies. This study developed a targeted delivery system using folic acid and Arginylglycylaspartic acid (RGD)-modified niosomes to deliver hydrophilic imatinib mesylate (IM) and hydrophobic curcumin (C) to treat breast cancer. The formulations were prepared and characaterized for size, zet potential, polydispersity index, % entrapment efficiency, and morphology. Moreover, FTIR (Fourier Transform Infrared) study negated incompatibility. <i>In vitro</i> drug release study was carried out at two different pH. <i>In vitro</i> cytotoxicity (dose dependent and ROS activity) and <i>in vivo</i> bioavailability studies were conducted to generate a proof of concept. The dual drug-loaded niosomal vesicles (R-F-PL64oxNS@IM-C) were designed for effective delivery of IM and C having particle size (&lt; 300 nm) with high zeta potential (- 18 mV). The formulation achieved high entrapment efficiency (&gt;70%) for both drugs with sustained release over 36 h at the explored two pH. <i>In vitro</i> results using MCF- 7 cells revealed significant cell death by R-F-PL64oxNS@IM-C as compared to pure drugs (IM &amp; C) through upregulation and downregulation of proapoptotic and antiapoptotic genes, respectively. <i>In vivo</i> studies showed approximately 1.9- and 5-fold higher biodistribution of C and IM, respectively using targeted niosomal systems as compared to pure drugs. The pharmacokinetic analysis revealed that Cmax and AUC of IM from R-F-PL64oxNS@IM and C from R-F-PL64oxNS@IM-C were significantly higher compared to pure IM and curcumin. Moreover, the Tmax had also increased for both IM (3 h) and C (3 h) using RGD and folic acid guided niosomal formulation suggesting its enhanced retention in systemic circulation leading to more bioavailability as compared to IM (0.5 h) and C (0.5 h). The targeted delivery also led to significant reduction in TNF-α levels, indicating improved therapeutic potential. The developed R-F-PL64oxNS@IM-C shown more precisely killing of breast cancer cell than pure IM and C.</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":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888667","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-Responsive Niosomal In Situ Gels for Topical Delivery of Prednisolone","authors":"Rania Hamed,&nbsp;Rafa Aburayya,&nbsp;Ahlam Zaid Alkilani,&nbsp;Alaa M. Hammad,&nbsp;Osama H. Abusara,&nbsp;Hadeel Abo-Zour","doi":"10.1208/s12249-025-03105-8","DOIUrl":"10.1208/s12249-025-03105-8","url":null,"abstract":"<div><p>Prednisolone (PRD) is known for its anti-inflammatory effect on the skin. The study aimed to encapsulate PRD into niosomes and then load them into thermo-responsive <i>in situ</i> gels for skin inflammation to enhance drug stability, skin permeability, and patient compliance while minimizing systemic exposure. PRD was encapsulated into non-PEGylated and PEGylated niosomes and then loaded into thermo-responsive <i>in situ</i> gels. The non-PEGylated PRD niosomes exhibited a particle size (PS) of 354.3 ± 1.9 nm, a polydispersity index (PDI) of 0.3 ± 0.0, and a ζ-potential of - 19.4 ± 1.0 mV. While the PEGylated attained PS, PDI, and ζ-potential of 314.9 ± 4.2 nm, 0.1 ± 0.0, and - 34.6 ± 2.2 mV, respectively. In addition, PEGylated niosomes exhibited higher entrapment efficiency and drug loading than non-PEGylated niosomes. The loading of the non-PEGylated and PEGylated PRD niosomes into thermo-responsive <i>in situ</i> gel showed a phase transition (T_sol→gel) at 34.1 ± 0.4 and 33.2 ± 0.9°C, respectively. The <i>in situ</i> gels showed a pseudoplastic flow with viscoelastic properties. The PRD niosomes and their corresponding <i>in situ</i> gels were biocompatible against human gingival fibroblasts. A decrease in rat paw inflammation was observed after applying the PRD niosomal gels. Stability studies for 3 months at 4°C showed that the PEGylated PRD niosomes and their corresponding <i>in situ</i> gel were more stable than the non-PEGylated PRD niosomes and their corresponding <i>in situ</i> gel. In conclusion, PEGylated PRD niosomal <i>in situ</i> gel demonstrated superior stability and sustained release, making it a promising candidate for topical corticosteroid 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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888695","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}