Pharmaceutics Division, Central Drug Research Institute, CSIR, Chattar Manzil Palace, M.G. Marg, Lucknow, 226001, India.
AAPS PharmSciTech. 2011 Mar;12(1):344-53. doi: 10.1208/s12249-011-9593-2. Epub 2011 Feb 1.
The aim of the study was to develop ultrathin polyelectrolyte microreservoir (UPM) using two combinations of synthetic/synthetic (S/s; poly(allylamine hydrochloride) (PAH)/sodium poly(styrenesulfonate)) and synthetic/natural (S/n; PAH/sodium alginate) polyelectrolytes over spherical porous CaCO(3) core particles (CP) followed by core removal and to evaluate its biocompatibility and integrity of loaded model protein bovine serum albumin (BSA). A novel process for synthesis of CP was developed to obtain maximum yield of monodisperse vaterite (spherical) polymorph. The prepared UPM was characterized for surface morphology, layer-by-layer growth, pay load efficiency, integrity of BSA, as well as viability and cell adhesion using murine J 774 macrophages (Φ). In vitro release profile revealed that both S/s and S/n UPM were able to provide sufficient diffusion barrier to release protein at physiological pH. It has been observed that S/n UPM are fully biocompatible due to obvious reason of using natural polymer. In a separate experiment, the S/s UPM surface was modified with pluronic F-68 to tune biocompatibility which provides evidences for safety and tolerability of the S/s UPM as well. In nutshell, the proposed system could successfully be used for the delivery of proteins, and moreover, the system can be tailored to impart desired properties at any stage of layering especially in terms of drug release and to retain the integrity of proteins.
本研究的目的是开发超薄膜状聚电解质微储器(UPM),使用两种组合的合成/合成(S/s;聚(盐酸烯丙胺)(PAH)/ 聚(苯乙烯磺酸钠))和合成/天然(S/n;PAH/ 海藻酸钠)聚电解质在球形多孔 CaCO3 核粒子(CP)上进行层层自组装,随后去除核,以评估其生物相容性和负载模型蛋白牛血清白蛋白(BSA)的完整性。开发了一种新型 CP 合成工艺,以获得最大的单分散水钙石(球形)多晶型产量。对制备的 UPM 进行了表面形貌、层层生长、载药量效率、BSA 完整性以及使用小鼠 J774 巨噬细胞(Φ)的活力和细胞黏附性进行了表征。体外释放结果表明,S/s 和 S/n UPM 均能够在生理 pH 值下提供足够的扩散屏障来释放蛋白质。由于使用天然聚合物的明显原因,S/n UPM 具有完全的生物相容性。在另一个实验中,用 Pluronic F-68 对 S/s UPM 表面进行修饰,以调整其生物相容性,这为 S/s UPM 的安全性和耐受性提供了证据。总之,所提出的系统可成功用于蛋白质的递送,并且该系统可在分层的任何阶段进行定制以赋予所需的特性,特别是在药物释放方面,并保持蛋白质的完整性。