通过基于聚合物的口腔给药提高依非韦伦的生物利用度:纳米晶体负载溶解微针给药系统的优化与表征。

IF 3.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Khairiyah Khairiyah, Muh Bisfain Asaf, Nur Afni Annisa Achmad, Rachmatya W Tuna, Irfan Kurniawan, Anugerah Yaumil Ramadhani Aziz, Maria Mir, Juan Domínguez-Robles, Mónica Millán-Jiménez, Ilyas Essadki-Aittaji, Ana B Cobo-González, Muhammad Aswad, Latifah Rahman, Marianti A Manggau, Aliyah Aliyah, Eyman Mohamed Eltayib, Andi Dian Permana
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引用次数: 0

摘要

依非韦伦(EFV)是一种广泛应用于艾滋病毒/艾滋病治疗的抗逆转录病毒药物,以其疗效而闻名,但也与各种副作用有关。为了改善药物给药,口腔给药是一种很有前途的选择,它允许药物直接通过口腔黏膜进入体循环,绕过胃肠道和第一过代谢。本研究通过分子对接探索了EFV与不同聚合物的相互作用,发现EFV与Pluronic®F-127具有较强的结合亲和力(-2.1 kcal/mol)。以Pluronic®F-127为稳定剂制备EFV纳米晶(EFV- nc),平均粒径为174.83±15.21 nm,粒径分布窄(PDI为0.15±0.013),稳定性好(zeta电位为-22.27±1.12 mV)。红外光谱(FTIR)和x射线衍射(XRD)分析表明,聚合物引起了EFV晶体结构的改变。EFV-NC提高了溶解度(高达400µg/mL),在24 h内达到89.58±4.01%的药物释放,符合Higuchi模型释放动力学。efv - nc负载溶解微针(EFV-NC-DMN)表现出强大的机械性能,有效的组织渗透和最小的吸湿性。体外和体内研究显示,与口服EFV相比,EFV- nc - dmn的相对生物利用度为137.40%,具有较高的血浆浓度和较长的释放时间,突出了其通过口腔给药改善HIV/AIDS治疗和改善治疗结果的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhancing Efavirenz Bioavailability Via Polymer-Based Buccal Administration: Optimization and Characterization of Nanocrystal-Loaded Dissolving Microneedle Delivery Systems.

Efavirenz (EFV) is a widely utilized antiretroviral agent in HIV/AIDS therapy that is known for its efficacy but is also associated with various side effects. For improved drug delivery, buccal administration offers a promising alternative by allowing the drug to enter the systemic circulation directly through the oral mucosa, bypassing the gastrointestinal tract and first-pass metabolism. This study explored the interaction between EFV and different polymers through molecular docking, revealing a strong binding affinity to Pluronic®F-127 (-2.1 kcal/mol). EFV was formulated into nanocrystals (EFV-NC) using Pluronic®F-127 as the stabilizer, characterized by an average particle size of 174.83 ± 15.21 nm, a narrow size distribution (PDI of 0.15 ± 0.013), and good stability (zeta potential of -22.27 ± 1.12 mV). FTIR and XRD analyses revealed polymer-induced alterations in the crystalline structure of the EFV. The EFV-NC formulation enhanced the solubility (up to 400 µg/mL) and achieved 89.58 ± 4.01% drug release within 24 h, following the Higuchi model kinetics for controlled release. EFV-NC-loaded dissolving microneedles (EFV-NC-DMN) demonstrated robust mechanical properties, efficient tissue penetration, and minimal moisture absorption. Ex vivo and in vivo studies revealed that compared with oral EFV, EFV-NC-DMN provided a relative bioavailability of 137.40%, with higher plasma concentrations and prolonged release, highlighting its potential for superior HIV/AIDS management via buccal administration and improved therapeutic outcomes.

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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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