AAPS PharmSciTech最新文献

{"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}

{"title":"Dual-Responsive Ion-Exchange Resin Encapsulated Atomoxetine Hydrochloride for Taste-Masking and Biphasic Release","authors":"Tao Xiao,&nbsp;Quanzhu Yang,&nbsp;Lusi Chen,&nbsp;Jiayu Xie,&nbsp;Huiying Zhong,&nbsp;Guoqing Zhang,&nbsp;Haibing He,&nbsp;Hongfei Liu","doi":"10.1208/s12249-025-03111-w","DOIUrl":"10.1208/s12249-025-03111-w","url":null,"abstract":"<div><p>Atomoxetine hydrochloride (ATH) is a first-line medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children. However, it poses challenges such as a bitter taste and difficulties in dose adjustment. While once-daily administration may result in excessive drug exposure, twice-daily dosing improves plasma drug concentration stability but can reduce patient compliance, especially in school-aged children. To address these challenges, a novel strategy was proposed that involves encapsulating ATH into ion exchange resins (IERs) (referred to as ATH@IER). The pH-responsive release of ATH from the ATH@IER exhibited a limited release rate in neutral conditions, effectively masking the bitter taste, which was evaluated through electronic tongue analysis. The cation-responsive release of ATH from the ATH@IER demonstrated immediate-release (IR) property, which was combined with Eudragit^® RS100 coated ATH@IER (ATH@MC) to establish a biphasic release system. ATH orally disintegrating tablets (ATH ODT) were manufactured using a composition of ATH@IER and ATH@MC (40:60, w/w), along with other excipients. Pharmacokinetic studies demonstrated that a single dose of ATH ODT produced a bimodal plasma concentration, resulting in a two-fold decrease in peak concentration (C_max) while maintaining an unchanged area under the drug concentration–time curve (AUC_0-t) compared to the commercial ATH oral solution administered once. Notably, the plasma drug concentration of ATH ODT remained steadier than that of the commercial product when administered twice. In conclusion, ATH ODT represents a promising formulation that effectively masks bitter taste and provides biphasic release for the treatment of ADHD.</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":"143888696","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":"Isotretinoin-Loaded Topical Lipid Liquid Crystal for the Treatment of Acne: In-Vitro and In-Vivo Evaluations","authors":"Armita Sedighidarijani,&nbsp;Shiva Golmohammadzadeh,&nbsp;Hossein Kamali,&nbsp;Bahman Khameneh,&nbsp;Elham Khodaverdi,&nbsp;Ali Nokhodchi","doi":"10.1208/s12249-025-03106-7","DOIUrl":"10.1208/s12249-025-03106-7","url":null,"abstract":"<div><p>Effective acne treatment is critical due to its profound impact on physical and psychological well-being. It was shown that severe systemic side effects, including teratogenicity, ovarian reserve reduction, depression, dry skin, hypertriglyceridemia, and intracranial hypertension limited oral isotretinoin usage. Therefore, this study addresses these challenges by developing isotretinoin-loaded lipid liquid crystal (LLC-IT) nanoparticles for topical application, aiming to enhance localized delivery while minimizing systemic exposure. LLC-IT nanoparticles were prepared using a top-down method and evaluated for their physicochemical properties, photostability, cytotoxicity, antimicrobial activity, <i>in-vitro</i> drug release, and <i>in-vivo</i> therapeutic efficacy. A testosterone-induced acne mouse model was used to compare LLC-IT treatment with untreated and commercial isotretinoin gel-treated groups. LLC-IT nanoparticles exhibited a uniform particle size (69.57 ± 0.51 nm), low polydispersity index (0.264 ± 0.01), and stable zeta potential (- 19.3 ± 0.2 mV). High encapsulation efficiency (95% ± 3) and effective loading capacity (1.15% ± 0.13) were achieved. Drug release was diffusion-controlled with minimal UV-induced degradation. Stability assessments over 12 months confirmed consistent properties across varying storage temperatures. LLC-IT displayed significant antibacterial activity and reduced skin irritation in Draize tests compared to commercial gels. <i>In-vivo</i>, LLC-IT reduced inflammation significantly more than untreated or commercial gel-treated groups, indicating enhanced therapeutic efficacy of LLC-IT formulation. The isotretinoin-loaded lipid liquid crystal formulation shows superior stability and efficacy with reduced side effects compared to conventional treatments, offering a more effective and patient-friendly solution, as well as a promising alternative for industrial production in acne management.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03106-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888668","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":"Integration of Synchronizing In Silico, In Vitro, and In Vivo Strategies for the Development of Antipsoriatic Apremilast-loaded Nanostructured Lipid Carrier Embedded in Hydrogel","authors":"Nikita Patel,&nbsp;Aneri Desai,&nbsp;Bhavin Vyas,&nbsp;Pranav Shah,&nbsp;Mangrulkar Shubhada,&nbsp;Umekar Milind,&nbsp;Kamla Pathak,&nbsp;Mahavir Bhupal Chougule","doi":"10.1208/s12249-025-03103-w","DOIUrl":"10.1208/s12249-025-03103-w","url":null,"abstract":"<div><p>One of the major challenges in the psoriasis therapies is the systemic side effects. This research investigation intended to design, formulate, and characterize topical Apremilast (APR) nanostructured lipid carriers (NLCs) embedded hydrogel. APR-loaded NLCs were prepared using the hot melt ultrasonication technique using glyceryl monostearate (GMS) and Capmul^® MCM, followed by high-speed homogenization. The entrapment and size were 85.5 ± 2.1% and 242.5 ± 3.1 nm, respectively. Using molecular docking, the interactions between APR-GMS and APR-Capmul^® MCM were investigated. 3² factorial designs were used to optimize APR-loaded NLCs, employing a quality-by-design approach. The spherical shape of the nanocarriers was depicted in the SEM images of NLCs dispersion. With a regression value of 0.9745, the <i>in vitro</i> drug release of APR-NLCs dispersion matched the Higuchi model and demonstrated extended-release up to 28 hrs (99.0 ± 1.7%). An <i>in vitro</i> cellular toxicity depicted that formulation excipients had minimal effect, as cell viability was still &gt; 80% at concentrations of up to 30 µg/mL. APR-NLC hydrogel exhibited extended release up to 36 hrs (97.1 ± 0.8%), with diffusion as a release mechanism. Since there was no significant difference observed in viscosity (cp) or % CDR throughout 24 hrs at 5°, indicate APR-NLCs hydrogel was stable in a refrigerated condition. Compared to the positive control, APR liquid, and pure drug, APR-NLCs hydrogel showed a substantial decrease in PASI score. Topical APR-loaded NLCs embedded in Hydrogel enhanced efficacy in the imiquimod-induced psoriasis in the murine model found to be non-irritating with minimal systemic side effects. The findings imply that APR-loaded NLCs embedded in Hydrogel can be used topically to treat psoriasis by focusing on the skin's outer layers.</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":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875466","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":"Collagenase-functionalized Liposomes Based on Enhancing Penetration into the Extracellular Matrix Augment Therapeutic Effect on Idiopathic Pulmonary Fibrosis","authors":"Xiaoqing Liu,&nbsp;Xiaoling Dong,&nbsp;Zhen Peng,&nbsp;Cuihong Wang,&nbsp;Jianwei Wan,&nbsp;Min Chen,&nbsp;Chunli Zheng","doi":"10.1208/s12249-025-03112-9","DOIUrl":"10.1208/s12249-025-03112-9","url":null,"abstract":"<div><p>In this study, a quercetin-loaded liposome system modified with collagenase was developed to increase QU penetration in the ECM and improve IPF treatment. Quercetin-loaded long circulation liposome (QU-LP) and quercetin-loaded liposome modified with collagenase type I (QU-CLP) were prepared, followed by characterization of the encapsulation efficiency, particle size, morphology, and <i>in vitro</i> drug release. Their effect on the cytotoxicity of A549 cells was detected by the Cell Counting Kit-8, and the cellular uptake was investigated using cellular fluorescence imaging and flow cytometry. TGF-β1 induced A549 cell model was established to mimic pulmonary fibrosis to explore further the anti-pulmonary fibrosis effect of QU-CLP by CCK8 experiment. QU-CLP significantly improves the solubility and bioavailability of QU by encapsulating it in the internal cavity with a high encapsulation efficiency (EE%) of 92.86 ± 1.03%. Liposomes alleviate the influence of QU on normal A549 cell growth. Enhanced fluorescence intensity was observed in A549 cells treated with coumarin 6-labeled and collagenase-modified nanoliposomes (C6-CLP) after 4 h of incubation on the collagen matrix, confirming that collagenase-loaded liposomes could penetrate the collagen barrier and cells internalized more hydrophobic drug. The mean fluorescence intensity (MFI) of the C6-CLP group was 2.88 times that of the C6-labeled nanoliposomes (C6-LP). Moreover, QU-CLP significantly (**<i>P</i> &lt; 0.01) inhibited the proliferation of A549 cells stimulated by TGF-β1. QU-CLP has excellent potential for delivering QU with enhanced bioavailability, high cellular uptake efficiency, and improved therapeutic efficacy in IPF.</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":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875468","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":"Carboplatin Co-loaded 5-Fluorouracil Nanoparticles Conjugated with Trastuzumab for Targeted Therapy in HER2+ Heterogeneity Breast Cancer","authors":"Akshay Kumar Lunawat,&nbsp;Debanjan Mukherjee,&nbsp;Riya Shivgotra,&nbsp;Sarjana Raikwar,&nbsp;Ankit Awasthi,&nbsp;Amrinder Singh,&nbsp;Shamsher Singh,&nbsp;Shivani Chandel,&nbsp;Subheet Kumar Jain,&nbsp;Shubham Thakur","doi":"10.1208/s12249-025-03107-6","DOIUrl":"10.1208/s12249-025-03107-6","url":null,"abstract":"<div><p>Breast cancer, the second-most common cause of cancer-related deaths among women, remains a significant global health challenge. This study focuses on developing trastuzumab (TmAb)-functionalized chitosan nanoparticles (CS-NPs) co-loaded with carboplatin and 5-fluorouracil (5-FU) for targeted treatment of HER2-positive breast cancer. The NPs were prepared via the ionic gelation method, optimized using Design of Experimentation (DoE), and characterized for particle size, zeta potential, PDI, and entrapment efficiency. TmAb conjugation was achieved using NHS and EDC, and further characterization included TEM, syringeability, hemolytic toxicity, <i>in-vitro</i> release, <i>ex-vivo</i> cell line study, and <i>in-vivo</i> anti-cancer activity using the Ehrlich ascites carcinoma (EAC) model. The <i>in-vitro</i> release studies indicated enhanced drug release at pH 5.5 over 32 h and showed first-order kinetics. The TmAb-conjugated NPs demonstrated specificity and targeting in the SK-BR-3 cell line and significant anti-cancer activity in the EAC model, with the highest tumor inhibition rate of 85.19% compared to 58.12% for the drug solution. These findings highlight the potential of TmAb-conjugated NPs for targeted breast cancer therapy, offering improved drug delivery and therapeutic efficacy, paving the way for future clinical applications to reduce side effects and overcome the limitations of conventional chemotherapy.</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":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875467","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":"Proposals for Global Harmonization of Regulations for Testing of Spacers and Valved Holding Chambers for Pressurized Metered Dose Inhalers","authors":"Jolyon P. Mitchell","doi":"10.1208/s12249-025-03110-x","DOIUrl":"10.1208/s12249-025-03110-x","url":null,"abstract":"<div><p>Thought should be given to the desirability for similar approaches for the present transition to low global warming potential (LGWP) propellants for pressurized metered dose inhalers (pMDIs)  to be adopted by both European Medicines Agency (EMA) and the United States Food and Drug Administration  (FDA) for the performance testing of pMDIs that include the evaluation with an add-on spacer or valved holding chamber as part of the <i>in vitro</i> component for product registration. If such an add-on device was to be included as part of the registration package in either US or European regulatory environments, the content of United States Pharmacopeia (USP) chapter &lt;1602&gt; could support the process.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845659","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}