Double-layer dissolving microneedles for delivery of mesenchymal stem cell Secretome: Formulation, characterisation and skin irritation study

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Avelia Devina Calista Nainggolan , Pietradewi Hartrianti , Qonita Kurnia Anjani , Ryan F. Donnelly , Agus Budiawan Naro Putra , Katherine Kho , Arief Kurniawan , Rr. Kirana Andranilla , Shereen Angelina Rattu , Delly Ramadon
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Abstract

Regenerative therapy based on stem cells have been developed, focusing on either stem cell or secretome delivery. Most marketed cellular and gene therapy products are available as injectable dosage forms, leading to several limitations requiring alternative routes, such as the intradermal route. Microneedles, capable of penetrating the stratum corneum barrier, offer a potential alternative for intradermal delivery. This present study aimed to develop double-layer dissolving microneedles (DMN) for the delivery of freeze-dried mesenchymal stem cell secretome. DMNs were fabricated using a two-step casting method and composed of two polymer combinations: poly(vinyl pyrrolidone) (PVP) with poly(vinyl alcohol) (PVA) or PVP with sodium hyaluronate (SH). The manufactured DMNs underwent assessments for morphology, mechanical strength, in skin dissolution, protein content, in vitro permeation, in vivo skin irritation, and physical stability. Based on evaluations of morphology and mechanical strength, two formulas (F5 and F12) met acceptance criteria. Evaluation of protein content revealed that F12 (PVP-SH combination) had a higher protein content than F5 (PVP-PVA combination), 99.02 ± 3.24 μg and 78.36 ± 3.75 μg respectively. In vitro permeation studies showed that F5 delivered secretome protein by 100.84 ± 0.88%, while F12 delivered 99.63 ± 9.21% in 24 h. After four days of observation on Sprague-Dawley rat’s skin, no signs of irritation, such as oedema and redness, was observed after applying both formulations. The safety of using PVP-PVA and PVP-SH combinations as excipients for DMN secretome delivery has been confirmed, promising significant advancements in biotherapeutic development in the future.

Abstract Image

用于递送间充质干细胞 Secretome 的双层溶解微针:配方、特性和皮肤刺激性研究
以干细胞为基础的再生疗法已经开发出来,主要集中在干细胞或分泌物的输送上。市场上销售的大多数细胞和基因治疗产品都是注射剂型,这导致了一些限制,需要采用其他途径,如皮内途径。微针能够穿透角质层屏障,为皮内给药提供了一种潜在的替代途径。本研究旨在开发用于递送冻干间充质干细胞分泌物的双层溶解微针(DMN)。DMN采用两步铸造法制造,由两种聚合物组合组成:聚乙烯吡咯烷酮(PVP)与聚乙烯醇(PVA)或PVP与透明质酸钠(SH)。生产出的 DMN 接受了形态、机械强度、皮肤溶解度、蛋白质含量、体外渗透性、体内皮肤刺激性和物理稳定性等方面的评估。根据对形态和机械强度的评估,两种配方(F5 和 F12)符合验收标准。蛋白质含量评估显示,F12(PVP-SH 组合)的蛋白质含量高于 F5(PVP-PVA 组合),分别为 99.02 ± 3.24 μg 和 78.36 ± 3.75 μg。体外渗透研究表明,在 24 小时内,F5 的分泌组蛋白渗透率为 100.84 ± 0.88%,而 F12 的渗透率为 99.63 ± 9.21%。对 Sprague-Dawley 大鼠皮肤进行四天观察后,两种制剂均未出现水肿和发红等刺激症状。将 PVP-PVA 和 PVP-SH 组合作为 DMN 分泌体递送辅料的安全性已得到证实,有望在未来的生物治疗开发中取得重大进展。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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