开发抗人类免疫缺陷病毒（HIV）纳米药物递送系统和释放方式，改善抗HIV药物的生物利用度，并减少不良反应。

通过水油水乳化和蒸发技术，抗病毒药物依非韦伦、替诺福韦酯和拉米夫定（重量比2︰1︰1）与聚乳酸-羟基乙酸共聚物（PLGA）及壳聚糖混合制备PLGA和聚乳酸-羟基乙酸共聚物-壳聚糖（PLGA-CS）载药纳米颗粒。PLGA和PLGA-CS载药纳米颗粒的粒径、多分散性分布指数和ζ-电位等进行表征，应用高效液相色谱（HPLC）探讨PLGA和PLGA-CS药物载量、包封率和药物释放，体外细胞试验分析生物相容性和细胞毒性。

PLGA-CS和PLGA颗粒粒径均一性好，经CS修饰PLGA-CS粒径由（198.2 ± 2.3）nm增加至（219.8 ± 6.5）nm，且与扫描电子显微镜（SEM）结果一致。经CS修饰后ζ-电位由（－25 ± 1.6）mV增加至（23.5 ± 1.9）mV。抗病毒药物包封效率由49%~52%增加至68%~77%。4 ℃和25 ℃下存储2个月PLGA-CS纳米颗粒药物保持量均> 90%，提示PLGA-CS载药纳米颗粒稳定性好。PLGA-CS初始暴发性释放减少，24 h内释放不足20%，与PLGA相比PLGA-CS的释放更长久。MTT实验发现，与PLGA-CS共培养的细胞活力均> 91.2%，且不依赖纳米颗粒浓度，提示PLGA-CS细胞毒性低生物相容性高。

PLGA-CS对抗HIV药物封装率高、稳定性好、无毒，且具有持续释放药物和增强药物疗效的优点，这为HIV感染者临床给药提供了一种新思路。

To develop a new nano-drug delivery system, to improve bioavailability and reduce adverse effect of antiretroviral drugs for human immunodeficiency virus (HIV).

Nano-drug delivery system produced by awater-oil-water emulsion and solvent evaporation technique was prepared by mixing anti-viral drug: efavirenz (EFV), tenofovir (TDF) and lamivudine (LAM) (weight ratio of 2︰1︰1) with poly (lactic-co-glycolic acid) (PLGA) and PLGA-chitosan (PLGA-CS). The drug-loaded nanoparticles were characterized for their particle size, poly-dispersity index and ζ-potential. The drug loading, encapsulation efficiency and drug release of PLGA and PLGA-CS nanoparticles were analyzed by high-performance liquid chromatography (HPLC). In vitro, cell viability was performed to evaluate biocompatibility and cytotoxicity.

Both PLGA-CS and PLGA nanoparticles exhibit good uniformity in particle size. Due to be coated with CS, the particle size of PLGA-CS nanoparticle was increased from (198.2 ± 2.3) nm to (219.8 ± 6.5) nm; the ζ-potential was increased from (-25.0 ± 1.6) mV to (23.5 ± 1.9) mV; drug encapsulation efficiency was increased from 49%-52% to 68%-77%. After a 2-month storage at 4 ℃ or 25 ℃, the drug retention of PLGA-CS nanoparticles remained above 90%. These results confirmed the excellent stability of PLGA-CS nanoparticles. The initial burst release of the antiretroviral drug from PLGA-CS nanoparticles exhibited a significant reduction, with the drug release remaining below 20% within 24 hours. The results in vitro studies pointed to the prolonged antiviral activity of AR-PLGA-CS. The stability of PLGA-CS was better than PLGA. Regardless of the concentration of PLGA-CS nanoparticles, the MTT assay showed that the cell viability was higher than 90%. This result indicated that PLGA-CS nanoparticles have low toxicity and excellent biocompatibility.

PLGA-CS nanoparticles exhibited high drug encapsulation efficiency, excellent stability, and the capacity of sustained drug release and enhanced therapeutic efficacy. This provides a new way for the clinical administration of antiretroviral drugs to patients with HIV infection.