Kang Bong-Seok, Lee Sang-Eun, Ng Choon Lian, Kim Jin-Ki, Park Jeong-Sook
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Korea.
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Korea.
Materials (Basel). 2015 Feb 5;8(2):486-498. doi: 10.3390/ma8020486.
The objective of this study was to improve the solubility of albendazole and optimize the preparation of an oral nanoparticle formulation, using β-cyclodextrin (βCD) and chitosan-tripolyphosphate (TPP) nanoparticles. The solubility of albendazole in buffers, surfactants, and various concentrations of acetic acid solution was investigated. To determine drug loading, the cytotoxic effects of the albendazole concentration in human hepatocellular carcinoma cells (HepG2) were investigated. The formulations were prepared by mixing the drug solution in Tween 20 with the chitosan solution. TPP solution was added dropwise with sonication to produce a nanoparticle through ionic crosslinking. Then the particle size, polydispersity index, and zeta potential of the nanoparticles were investigated to obtain an optimal composition. The solubility of albendazole was greater in pH 2 buffer, Tween 20, and βCD depending on the concentration of acetic acid. Drug loading was determined as 100 µg/mL based on the results of cell viability. The optimized ratio of Tween 20, chitosan/hydroxypropyl βCD, and TPP was 2:5:1, which resulted in smaller particle size and proper zeta positive values of the zeta potential. The chitosan-TPP nanoparticles increased the drug solubility and had a small particle size with homogeneity in formulating albendazole as a potential anticancer agent.
本研究的目的是提高阿苯达唑的溶解度,并使用β-环糊精(βCD)和壳聚糖-三聚磷酸钠(TPP)纳米颗粒优化口服纳米颗粒制剂的制备。研究了阿苯达唑在缓冲液、表面活性剂和不同浓度乙酸溶液中的溶解度。为了确定载药量,研究了阿苯达唑浓度对人肝癌细胞(HepG2)的细胞毒性作用。通过将吐温20中的药物溶液与壳聚糖溶液混合来制备制剂。滴加TPP溶液并进行超声处理,通过离子交联产生纳米颗粒。然后研究纳米颗粒的粒径、多分散指数和zeta电位,以获得最佳组成。根据乙酸浓度的不同,阿苯达唑在pH 2缓冲液、吐温20和βCD中的溶解度更大。根据细胞活力结果,确定载药量为100μg/mL。吐温20、壳聚糖/羟丙基βCD和TPP的优化比例为2:5:1,这导致粒径更小,zeta电位具有合适的正数值。壳聚糖-TPP纳米颗粒提高了药物溶解度,并且在将阿苯达唑制备成潜在抗癌剂时具有小粒径和均一性。