Targeted Delivery of PSC-RANTES for HIV-1 Prevention using Biodegradable Nanoparticles
Targeted Delivery of PSC-RANTES for HIV-1 Prevention using Biodegradable Nanoparticles
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DOI：
10.1007/s11095-008-9765-2
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发表时间：
2009-03-01
影响因子：
3.7
通讯作者：
Rohan, Lisa Cencia
中科院分区：
文献类型：
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作者：
Ham, Anthony S.;Cost, Marilyn R.;Rohan, Lisa Cencia
由可生物降解的共聚物聚乳酸-羟基乙酸（PLGA）制成的纳米颗粒被研究作为一种药物传递系统，以增强PSC-RANTES抗hiv -1活性的组织摄取、渗透和靶向性。PSC-RANTES纳米颗粒通过双乳工艺配制，并在体外和离体系统中进行表征，以确定PSC-RANTES释放率、纳米颗粒组织渗透和抗hiv生物活性。制备了球形单分散（PDI = 0.098 +/- 0.054） PSC-RANTES纳米颗粒（d = 256.58 +/- 19.57 nm），包封效率为82.23 +/- 8.35%。体外释放研究表明PSC-RANTES具有控释谱（71.48 +/- 5.25%释放）。在基于HeLa细胞的系统中，PSC-RANTES纳米颗粒与未配制的PSC-RANTES保持相当的抗hiv活性，IC50约为1pM。在离体宫颈组织模型中，与未配制的PSC-RANTES相比，PSC-RANTES纳米颗粒的组织摄取增加了5倍，组织渗透增强，并且在上皮基底层有明显的定位。这些结果表明，PSC-RANTES可以很容易地被封装到PLGA纳米颗粒药物递送系统中，保持其抗hiv -1活性，并将PSC-RANTES递送到目标组织。这对于该候选药物作为局部杀微生物剂产品的成功至关重要。
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 IC50 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.