Ham Anthony S, Cost Marilyn R, Sassi Alexandra B, Dezzutti Charlene S, Rohan Lisa Cencia
Magee-Womens Research Institute, 204 Craft Avenue, B509, Pittsburgh, Pennsylvania, 15213, USA.
Pharm Res. 2009 Mar;26(3):502-11. doi: 10.1007/s11095-008-9765-2. Epub 2008 Nov 11.
Nanoparticles formulated from the biodegradable co-polymer poly(lactic-co-glycolic acid) (PLGA), were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting for PSC-RANTES anti-HIV-1 activity.
PSC-RANTES nanoparticles formulated via a double emulsion process and characterized in both in vitro and ex vivo systems to determine PSC-RANTES release rate, nanoparticle tissue permeation, and anti-HIV bioactivity.
Spherical, monodisperse (PDI = 0.098 +/- 0.054) PSC-RANTES nanoparticles (d = 256.58 +/- 19.57 nm) with an encapsulation efficiency of 82.23 +/- 8.35% were manufactured. In vitro release studies demonstrated a controlled release profile of PSC-RANTES (71.48 +/- 5.25% release). PSC-RANTES nanoparticle maintained comparable anti-HIV activity with unformulated PSC-RANTES in a HeLa cell-based system with an IC(50) of approximately 1pM. In an ex vivo cervical tissue model, PSC-RANTES nanoparticles displayed a fivefold increase in tissue uptake, enhanced tissue permeation, and significant localization at the basal layers of the epithelium over unformulated PSC-RANTES.
These results indicate that PSC-RANTES can readily be encapsulated into a PLGA nanoparticle drug delivery system, retain its anti-HIV-1 activity, and deliver PSC-RANTES to the target tissue. This is crucial for the success of this drug candidate as a topical microbicide product.
研究由可生物降解共聚物聚乳酸-羟基乙酸共聚物（PLGA）制成的纳米颗粒作为药物递送系统，以增强组织摄取、渗透和对PSC-RANTES抗HIV-1活性的靶向性。
通过复乳法制备PSC-RANTES纳米颗粒，并在体外和体内系统中进行表征，以确定PSC-RANTES的释放速率、纳米颗粒的组织渗透和抗HIV生物活性。
制备出了球形、单分散（PDI = 0.098 ± 0.054）的PSC-RANTES纳米颗粒（d = 256.58 ± 19.57 nm），包封率为82.23 ± 8.35%。体外释放研究表明PSC-RANTES具有控释特性（释放率为71.48 ± 5.25%）。在基于HeLa细胞的系统中，PSC-RANTES纳米颗粒与未制成纳米颗粒的PSC-RANTES保持相当的抗HIV活性，IC(50)约为1pM。在体内宫颈组织模型中，与未制成纳米颗粒的PSC-RANTES相比，PSC-RANTES纳米颗粒的组织摄取增加了五倍，组织渗透增强，并且在上皮层基底层有显著定位。
这些结果表明，PSC-RANTES可以很容易地被包裹到PLGA纳米颗粒药物递送系统中，保留其抗HIV-1活性，并将PSC-RANTES递送至靶组织。这对于这种候选药物作为局部杀菌剂产品的成功至关重要。
