AAPS PharmSciTech最新文献

{"title":"Integrating Quantitative Methods & Modeling and Analytical Techniques in Reverse Engineering; A Cutting-Edge Strategy in Complex Generic Development","authors":"Akash Rajput,&nbsp;Megha Pillai,&nbsp;Jinal Ajabiya,&nbsp;Pinaki Sengupta","doi":"10.1208/s12249-025-03067-x","DOIUrl":"10.1208/s12249-025-03067-x","url":null,"abstract":"<div><p>Generic drugs are crucial for healthcare, offering affordable alternatives to brand-name drugs. Complex generics, with intricate ingredients, are gaining increasing importance in managing chronic conditions. However, prior to the regulatory market approval, they must demonstrate similarity in active ingredients, formulations, strength, and administration routes to ensure bioequivalence. The primary constraint lies in demonstrating bioequivalence with the innovator drug using traditional methods includes a lack of advanced technologies, and standardized protocols for analysing complex products. Given the multifaceted nature of these products, a single methodology may not suffice to establish <i>in vitro</i>/<i>in vivo</i> bioequivalence. Recognizing this, the USFDA conducts several workshops aiming advancement of complex generic drug product development. Notably, these efforts highlight the need to use Quantitative Methods and Modeling (QMM) approaches to support generic product development. QMM is a scientific approach used to analyze data and simulate drug development processes, ensuring safe, effective, and similar formulations of generic drugs using mathematical, statistical, and computational tools. QMM facilitates the design of formulations and processes, establishes a framework for <i>in vivo</i> BE studies, and suggests alternative ways to demonstrate BE. Appropriate utilization of the QMM approach can reduce the need for unwanted <i>in vivo</i> studies and bolster <i>in vitro</i> approaches for generic product development. Furthermore, use of orthogonal analytical techniques to characterize and decode innovator drugs can provide valuable insights into product attributes. Integrating this data into QMM enables the assessment of critical material attributes, or critical process parameters, thus demonstrating sameness. The combined application of QMM and analytical techniques not only supports regulatory decisions but also enhances the success rate of complex generic drug products.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706929","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":"Co-Delivery of Tacrolimus and Thymoquinone Topically by Nanostructured Lipid Carrier Gel for Enhanced Efficacy Against Psoriasis","authors":"Meraj Alam,&nbsp;Md. Rizwanullah,&nbsp;Shahnawaz Ahmad,&nbsp;Ashif Iqubal,&nbsp;Showkat R. Mir,&nbsp;Tae-Geum Kim,&nbsp;Saima Amin","doi":"10.1208/s12249-025-03074-y","DOIUrl":"10.1208/s12249-025-03074-y","url":null,"abstract":"<div><p>Psoriasis is a chronic inflammatory skin disorder affecting 2–5% of the global population and is often characterized by skin thickening, scaling, and various epidermal changes. Current topical treatments have limitations in terms of efficacy, skin penetration, and side effects. The present study aimed to develop a novel nanostructured lipid carrier (NLC) gel that co-encapsulates tacrolimus (TAC) and thymoquinone (THQ) to enhance drug delivery and efficacy in the treatment of psoriasis. TAC-THQ-NLC was formulated using the emulsification solvent-evaporation technique and subsequently converted into nanogel using Carbopol Ultrez10 as a gelling agent. The prepared nanogel efficacy was evaluated through <i>ex-vivo</i> skin permeation, dermatokinetic analysis, and psoriasis-induced Balb/c mice model. The TAC-THQ-NLC-gel (TAC-THQ-NG) demonstrated significantly higher skin permeation compared to the TAC-THQ-suspension-gel (TAC-THQ-SG). Specifically, the permeation enhancement for the NLC-gel was 2.51-fold and 2.12-fold for TAC and THQ, respectively. These enhancements were confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The dermatokinetic analysis showed that the TAC-THQ-NG had 2.78-fold and 2.37-fold higher maximum concentration (C_max) and 2.93-fold and 2.40-fold higher area under the curve (AUC) for TAC and THQ, respectively, compared to the TAC-THQ-SG. Further, in the Balb/c mice psoriasis model, the TAC-THQ-NG formulation resulted in an 83.80 ± 3.62% reduction in the cumulative Psoriasis Area Severity Index (PASI) score of thickness, erythema, and scaling, compared to the TAC-THQ-SG formulation, which showed 57 ± 9.90% reduction. The results of the <i>in vivo</i> skin compliance study suggested that the developed TAC-THQ-NG was safe for topical application. Further histopathological examination showed no significant changes in the skin, spleen, and liver, indicating the efficacy and safety of the TAC-THQ-NG formulation. Based on these observations, it can be inferred that the developed TAC-THQ-NG exhibits superior therapeutic efficacy.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698686","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":"Treatment of Bleomycin-induced Pulmonary Fibrosis by Intratracheal Instillation Administration of Ellagic Acid-Loaded Chitosan Nanoparticles","authors":"Zhilin Luo,&nbsp;Yao Sun,&nbsp;Shihao Cai,&nbsp;Hongting Liu,&nbsp;Conglu Zhao,&nbsp;Xiang Xu,&nbsp;Aiguo Xu,&nbsp;Honggang Zhou,&nbsp;Cheng Yang,&nbsp;Xiaoting Gu,&nbsp;Xiaoyu Ai","doi":"10.1208/s12249-025-03086-8","DOIUrl":"10.1208/s12249-025-03086-8","url":null,"abstract":"<div><p>Idiopathic Pulmonary Fibrosis (IPF) is a rare and serious chronic interstitial lung disease that may endanger the lives of patients. The median survival time of patients with idiopathic pulmonary fibrosis is short, and the mortality rate is higher than that of many types of cancer. At present, pirfenidone (PFD) and nintedanib (NDNB) have been approved by FDA for IPF, but they can only delay the process of pulmonary fibrosis and cannot cure the disease. Therefore, it is urgent to develop other drugs with the effect of improving pulmonary fibrosis. Ellagic acid (EA) can inhibit the Wnt-signaling pathway and has an effect in treating pulmonary fibrosis induced by bleomycin (BLM) in mice. However, its solubility is poor, resulting in its low bioavailability and limited therapeutic benefits, so its clinical application has been limited. Herein, based on the characteristics of nano-drug lung delivery system, chitosan (CS) was selected as the carrier, and ellagic acid-loaded chitosan nanoparticles (EA-CS-NPs) were prepared by ionic gelation method. The EE% and DL% of prepared EA-CS-NPs was 73.73 ± 4.52% and 6.23 ± 1.09%, the particle size was 119.6 ± 5.51 nm (PDI = 0.234 ± 0.017), the zeta potential was 29.833 ± 0.503 mV. The morphology of the nanoparticles was observed by TEM microscope, which was round, uniform dispersion, indicating that the preparation process is stable and feasible. The toxicity experiment showed that EA-CS-NPs maintained 80% cell viability, significantly higher than that of the NDNB group, indicating lower toxicity and better inhibitory effects on TGF-β1-stimulated MLg and NIH-3T3 cells. Wound healing assay results showed that the inhibitory effect of EA-CS-NPs on cell migration was more pronounced than that of EA in the same amount of EA-containing drugs. Drug uptake experiments revealed that EA-CS-NPs significantly enhanced drug uptake in MLg and NIH-3T3 cells. <i>In vivo</i>, Cy7-CS-NPs exhibited higher fluorescence intensity in rat lungs compared to Cy7 solution, indicating better lung retention. The <i>in vivo</i> efficacy test showed that compared with the EA group, EA-CS-NPs could better reduce the area of pulmonary fibrosis and collagen deposition, improve lung function, and have a longer retention time in the lung. In summary, our results revealed that EA-CS-NPs may be a good choice for the treatment of pulmonary fibrosis.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706926","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 of Complex Generics and Similar Biological Products: An Industrial Perspective of Reverse Engineering","authors":"Rajeev Ranjan","doi":"10.1208/s12249-025-03087-7","DOIUrl":"10.1208/s12249-025-03087-7","url":null,"abstract":"<div><p>Generic drugs are developed to be bioequivalent to innovator formulation, matching them in dosage form, safety, strength, quality and efficacy. Known as \"interchangeable multi-source pharmaceutical products,\" generics play a crucial role in reducing therapeutic costs and enhancing patient compliance. Over the past decade, generics have accounted for more than 90% of prescriptions in the U.S., which has driven down the average price of these drugs to nearly match production costs once market competition grows. Simple generics of small-molecule drugs are often produced through trial and error based on existing data, but complex generics require advanced techniques like reverse engineering to replicate the brand drug's release profile. These complex generics include sophisticated drug delivery forms that ensure the therapeutic agent is released gradually, maximizing effectiveness. Conversely, similar biological products highly similar to approved biologics-undergo rigorous analytical and clinical evaluations due to their complexity and the nature of biologic production. The increased demand for similar biological products is driven by expiring biologic patents, economic incentives, and regulatory advancements, with the market expected to grow significantly by 2026. The Biologic Price Competition and Innovation Act (BPCIA) enable abbreviated approvals for similar biological products, promoting affordability. Despite minor differences from original biologics, similar biological products undergo extensive testing to ensure safety and efficacy, following global regulatory guidelines that emphasize strict quality standards. This framework is essential for expanding patient access to effective therapies for conditions like cancer and autoimmune diseases while supporting healthcare sustainability.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706927","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":"Novel Methods Developed in Bioequivalence Assays: Patent Review","authors":"Brian Sebastian Correa Barrera,&nbsp;Izabel Almeida Alves,&nbsp;Diana Marcela Aragón","doi":"10.1208/s12249-025-03079-7","DOIUrl":"10.1208/s12249-025-03079-7","url":null,"abstract":"<div><p>This study examines advancements in bioequivalence (BE) assessment methods, with a focus on <i>in vitro</i>-<i>in vivo</i> correlation (IVIVC) and dissolution testing technologies. A systematic patent search was conducted via Espacenet, following PRISMA criteria and the study objectives, revealing 216 relevant patents, of which 28 were selected based on their contributions to novel BE methodologies. Analysis indicates a rapid increase in patent filings from 2021 to 2022, with a significant concentration of contributions from China. Key innovations include enhancements in dissolution testing apparatus, application of physiologically based pharmacokinetic (PBPK) modeling for IVIVC, and advanced statistical approaches for BE assessment. In dissolution testing, ƒ1 and ƒ2 factors remain essential metrics for assessing similarity, especially in solid oral dosage forms. These innovations enhance the efficiency (streamline) of BE evaluations, optimizing the biowaiver process and minimizing the need for extensive clinical trials while ensuring greater precision and reliability. The dissolution test, particularly when combined with PBPK models, allows for predictive evaluation of formulation changes and population-specific responses, fostering efficiency in drug development. Overall, these novel BE assessment approaches provide a framework for regulatory compliance, cost-effective production, and assurance of therapeutic equivalence in generic formulations. While they may not always be implemented in practice, they contribute significantly to innovation in the field, driving advancements in bioequivalence evaluation. This review highlights the evolving landscape of BE and IVIVC methodologies and underscores the importance of incorporating innovative testing approaches to advance pharmaceutical science and regulatory practices.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698685","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":"Engineering pH-Dependent Orally Disintegrating Tablets for Modified Indomethacin Release: A Polymer-Based Approach","authors":"Nihad Al-hashimi,&nbsp;Eman Zmaily Dahmash,&nbsp;Mouhamad Khoder,&nbsp;Raid Alany,&nbsp;Amr Elshaer","doi":"10.1208/s12249-025-03082-y","DOIUrl":"10.1208/s12249-025-03082-y","url":null,"abstract":"<div><p>The application of pH-sensitive polymers has been widely explored in pharmaceutical industry because of their versatile properties. This work aims to delay the release of indomethacin (IND), a commonly used anti-inflammatory drug, using a pH-dependent polymer within orally disintegrating tablets (ODTs) and to investigate the effect of the polymer particle size on the ODTs. When developing delayed-release formulations for orally disintegrating tablets (ODTs), it's essential to balance the pellet's matrix properties to maintain integrity and delayed release. Different sizes of Eudragit L100 were used to create IND-containing pellets via extrusion spheronization, which were then embedded into the matrix of ODTs. The particle sizes displayed good elastic properties with low Young's modulus (YM) values, and there was no significant difference between the different sizes (45, 60, 93 µm; <i>p</i> &gt; 0.05). The tensile strength of the pellets was directly proportional to YM (<i>p</i> &lt; 0.05), providing enough support to maintain their integrity under compression. Pellets made from 63 µm Eudragit L100 had a suitable balance of mechanical and pharmaceutical properties compared to other sizes. 63 µm pellets had an aspect ratio of 1.49 ± 0.26 and 61% yield, while their ODTs showed a fast disintegration time of 14 ± 0.6 s, while modifying the drug release. Furthermore, IND exhibited modified release in acidic media (pH 1.2) and immediate release in buffer media (pH 6.8). Overall, protecting pellet integrity was crucial to delay release in acidic media and enable immediate release in alkaline media. The newly developed formulation will improve compliance and reduce side effects associated with IND and other irritant drugs particularly in elderly populations.</p><h3>Graphical Abstract</h3><p>Graphical illustration for developing delayed release indomethacin loaded Eudragit L100 pellets embedded in orally disintegrating tablets\u0000</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03082-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706928","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":"Amorphous Solid Dispersion/Salt of Efavirenz: Investigating the Role of Molecular Interactions on Recrystallization and In-vitro Dissolution Performance","authors":"Aastha Gadoya,&nbsp;Kiran Dudhat,&nbsp;Sunny Shah,&nbsp;Chetan Borkhataria,&nbsp;Trupesh Pethani,&nbsp;Viral Shah,&nbsp;Nilesh Janbukiya,&nbsp;Saina Jyotishi,&nbsp;Jainabparvin Ansari,&nbsp;Mori Dhaval","doi":"10.1208/s12249-025-03084-w","DOIUrl":"10.1208/s12249-025-03084-w","url":null,"abstract":"<div><p>Efavirenz (EFZ), a BCS (Biopharmaceutical classification system) class-II/IV drug, suffers from low oral bioavailability (40–50%) and significant inter/intra-individual variability due to its low solubility and poor dissolution properties. The present investigation aimed to prepare a stable amorphous system of EFZ to improve its dissolution using the slurry method with various polymers and examine the nature of the interaction between them and its impact on the stability (recrystallization) of the formed systems and their <i>in-vitro</i> dissolution performance. Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies proved the formation of a complete amorphous system of EFZ with Eudragit® E100, HPMC E5, and HPMCAS-LF up to 50% drug loading. During 90 days accelerated stability studies, amorphous systems prepared using Eudragit® E100 remained stable at 50% drug loading however those prepared with HPMC E5, and HPMCAS-LF only remained stable at 25% drug loading. The ability of Eudragit® E100 based system to stabilize the drug at higher drug loading was attributed to the formation of stronger ionic interaction as revealed by the Fourier-transform infrared spectroscopy (FTIR) study. During <i>in-vitro</i> dissolution study, Eudragit® E100 based amorphous system generated and maintained significantly higher supersaturation compared to those prepared with HPMC E5, and HPMCAS-LF due to the formation of ionic interaction between EFZ and Eudragit® E100 as revealed by solution ¹H NMR study.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645407","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 Optimization of Eberconazole Nanostructured Lipid Carrier Topical Formulations Based on the QbD Approach","authors":"Amarnath Reddy Ramireddy,&nbsp;Dilip Kumar Behara","doi":"10.1208/s12249-025-03083-x","DOIUrl":"10.1208/s12249-025-03083-x","url":null,"abstract":"<div><p>Eberconazole nanostructured lipid carrier (EBR-NLC) 1% w/w optimization was done using the Quality by Design (QbD) approach, employing a 2³ Full Factorial Design (FFD) for experimental planning, followed by thorough physico-chemical, in-vitro, and ex-vivo evaluations. The 2³ FFD assessed the impact of total lipid amount, surfactant amount, and sonication time on critical quality attributes such as particle size and % entrapment efficiency. <i>In-vitro</i>release testing (IVRT) validation was performed using vertical diffusion cells. IVRT, a compendial technique by pharmacopoeias, was for performing semi-solid formulations analysis. The optimized EBR-NLC 1% w/w was characterized for assay, organic impurities, amplitude sweep, viscosity, IVRT, ex-vivo permeation testing, and skin retention. The validated IVRT technique was meeting the acceptance criteria of regulatory guidelines. The results showed that in-vitro release, ex-vivo permeation, and skin retention were significantly higher (<i>P</i> &lt; 0.05) for the optimized EBR-NLC 1% w/w formulation compared to the innovator formulation (EBERNET^® Cream 1% w/w). Applying QbD principles systematically facilitated the successful development and optimization of an EBR-NLC 1% w/w. The optimized EBR-NLC 1% w/w formulation proved to be a viable alternative, showing stability for at least six months under conditions of 40°C/75% RH and 30°C/75% RH.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645409","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":"Quantitative Analysis of Salmon Calcitonin Hydroxyapatite Nanoparticle Permeation to substantiate Non-Invasive Bone Targeting via Sublingual Delivery","authors":"Darsheen Kotak,&nbsp;Esha Attar,&nbsp;Bhavik Dalal,&nbsp;Aruna Shankarkumar,&nbsp;Padma Devarajan","doi":"10.1208/s12249-025-03068-w","DOIUrl":"10.1208/s12249-025-03068-w","url":null,"abstract":"<div><p>We earlier reported comparable efficacy in bone parameters of sublingually administered salmon calcitonin hydroxyapatite nanoparticles (SCT-HAP-NPs) compared to the subcutaneous injection, in the ovariectomy rat model, despite a bioavailability of barely ~ 15%. We ascribed this intriguing finding to targeted bone delivery, facilitated by translocation of significant quantity of intact NP into systemic circulation. In the present study we track the translocation of FITC-SCT-HAP-NPs (~ 100 nm) across porcine sublingual mucosa using the Franz diffusion cell to validate our hypothesis. Confocal Laser Scanning microscopy (CLSM) established that SCT-HAP-NPs permeated into the deeper layers of sublingual porcine mucosal tissue. We confirmed the nanoparticles were present in the receptor medium of the Franz diffusion cell by DLS and TEM. We also demonstrate for the first time quantification of the NPs (%) translocated across the porcine mucosa, using the Amnis Image StreamX Mk II imaging flow cytometer. Computation revealed transport of ~ 60% of the FITC-SCT-HAP-NPs across mucosa in 2 h, substantiated that high NP concentrations could reach systemic circulation. Such high NP concentration in systemic circulation coupled with the small size (~ 100 nm) and the high bone affinity of HAP, validate our hypothesis of targeted bone delivery following sublingual administration. Furthermore, quantification of translocated NPs, which we demonstrate for the first time, would permit rational development of optimal targeted nanoparticulate carriers for delivery by noninvasive routes.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645408","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":"Brazilian Green Propolis Extract-Loaded Poly(Ε-Caprolactone) Nanoparticles Coated with Hyaluronic Acid: Antifungal Activity in a Murine Model of Vulvovaginal Candidiasis","authors":"Aniely Dos Reis Teixeira,&nbsp;Amanda De Vasconcelos Quaresma,&nbsp;Renata Tupinambá Branquinho,&nbsp;Patrícia Capelari De Oliveira,&nbsp;Jorge Andrés García Suárez,&nbsp;Geraldo Célio Brandão,&nbsp;Ana Paula Moreira Barboza,&nbsp;Marcelo Gonzaga De Freitas Araújo,&nbsp;Juliana Teixeira De Magalhães,&nbsp;Sandra Aparecida Lima De Moura,&nbsp;Gisele Rodrigues Da Silva","doi":"10.1208/s12249-025-03081-z","DOIUrl":"10.1208/s12249-025-03081-z","url":null,"abstract":"<div><p>Brazilian green propolis extract-loaded poly(ε-caprolactone) nanoparticles coated with hyaluronic acid (PE-NPsHA) were developed as a therapeutic strategy to treat vulvovaginal candidiasis (VVC) and combat the growing issue of fungal resistance. The chemical composition of PE was analyzed using UHPLC-MS/MS, revealing the presence of various bioactive compounds, such as phenolic acids, flavonoids, coumarins, and quinones. These compounds were encapsulated into the polymeric matrix of NPs, as indicated by FTIR and DSC. In addition, PE-NPsHA were characterized by DLS, AFM, encapsulation efficiency (EE), and <i>in vitro</i> release study. They displayed a spherical morphology with a hydrodynamic diameter of 170 nm, a low polydispersity index of 0.1, a zeta potential of -28.5 mV, and an EE of 78%. The <i>in vitro</i> release study indicated a controlled and sustained release of PE over a period of 96 h. The <i>in vitro</i> and <i>in vivo</i> PE-NPsHA biocompatibility were investigated as well as their antifungal activity in a murine model of VVC. PE-NPsHA did not impact the HaCaT cell viability and demonstrated no signs of <i>in vivo</i> vaginal toxicity. PE-NPsHA exhibited <i>in vivo</i> antifungal efficacy, effectively eliminating <i>Candida albicans</i> infection. PE-NPsHA could expand the available treatment options for VVC and counteract <i>Candida</i> resistance to antifungal drugs.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621792","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}