Ernest Mario School of Pharmacy , Rutgers-The State University of New Jersey , 160 Frelinghuysen Road , Piscataway , New Jersey 08854 , United States.
Center for Dermal Research , Rutgers-The State University of New Jersey , 145 Bevier Roa , Piscataway , New Jersey 08854 , United States.
Mol Pharm. 2018 Sep 4;15(9):3813-3822. doi: 10.1021/acs.molpharmaceut.8b00318. Epub 2018 Jul 31.
In this study we aimed to develop a semi-solid formulation of polymeric nanoparticles loaded with adapalene to enhance the efficacy and improve the skin tolerability in acne therapy. An amphiphilic and biocompatible copolymer that self-assembles to nanospheres (known as TyroSpheres) was used to encapsulate adapalene and increase its solubility. A water-soluble viscous agent was applied to prepare a gel formulation of adapalene-loaded TyroSpheres (aapalene-TyroSphere). Particle size, morphology, homogeneity, and rheological characteristics of the adapalene-TyroSphere gel formulations were studied. The formulation with the preferred physical and structural properties was further investigated for in vitro skin irritation and in vivo comedolytic activity in a rhino mouse model. Based on the in vitro skin irritation study encapsulation of adapalene in TyroSphere significantly decreased secretion of pro-inflammatory cytokines (IL-1α and IL-8), confirming that the TyroSphere formulation of adapalene is less irritant than the commercial gel (Differin). TyroSphere gel formulation of adapalene improved the comedolytic properties of the formulation by significantly reducing the size of open utricles in rhino mice compared to Differin treatment. Using TyroSpheres, we were able to develop an alternative topical formulation of adapalene, which is potentially less irritant and more potent than the commercial product.
在这项研究中，我们旨在开发一种载有阿达帕林的聚合物纳米粒子半固体制剂，以提高疗效并改善痤疮治疗中的皮肤耐受性。我们使用一种两亲性和生物相容性的共聚物来包封阿达帕林并增加其溶解度，该共聚物自组装成纳米球（称为 TyroSpheres）。我们还应用一种水溶性粘性剂来制备载有阿达帕林的 TyroSphere（aapalene-TyroSphere）凝胶制剂。研究了阿达帕林-TyroSphere 凝胶制剂的粒径、形态、均一性和流变学特性。对具有优选物理和结构特性的制剂进一步进行了体外皮肤刺激性和在犀牛鼠模型中的体内去角质活性研究。基于体外皮肤刺激性研究，阿达帕林在 TyroSphere 中的包封显著降低了促炎细胞因子（IL-1α 和 IL-8）的分泌，这证实了阿达帕林 TyroSphere 制剂比商业凝胶（Differin）的刺激性更小。与 Differin 治疗相比，阿达帕林 TyroSphere 凝胶制剂显著减小了犀牛鼠开放小囊的大小，从而改善了制剂的去角质特性。使用 TyroSpheres，我们能够开发出一种潜在的阿达帕林替代局部制剂，其比商业产品的刺激性更小，效果更强。
