Mandal Bivash, Mittal Nivesh K, Balabathula Pavan, Thoma Laura A, Wood George C
Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, 3 N Dunlap Street, Memphis, TN 38163, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, 3 N Dunlap Street, Memphis, TN 38163, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
Eur J Pharm Sci. 2016 Jan 1;81:162-71. doi: 10.1016/j.ejps.2015.10.021. Epub 2015 Oct 27.
Core-shell type lipid-polymer hybrid nanoparticles (CSLPHNPs) have emerged as a multifunctional drug delivery platform. The delivery system combines mechanical advantages of polymeric core and biomimetic advantages of the phospholipid shell into a single platform. We report the development of CSLPHNPs composed of the lipid monolayer shell and the biodegradable polymeric core for the delivery of erlotinib, an anticancer drug, clinically used to treat non-small cell lung cancer (NSCLC). Erlotinib loaded CSLPHNPs were prepared by previously reported single-step sonication method using polycaprolactone (PCL) as the biodegradable polymeric core and phospholipid-shell composed of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000). Erlotinib loaded CSLPHNPs were characterized for physicochemical properties including mean particle size, polydispersity index (PDI), zeta potential, morphology, thermal and infrared spectral analysis, drug loading, in vitro drug release, in vitro serum stability, and storage stability. The effect of critical formulation and process variables on two critical quality attributes (mean particle size and drug entrapment efficiency) of erlotinib loaded CSLPHNPs was studied and optimized. In addition, in vitro cellular uptake, luminescent cell viability assay and colony formation assay were performed to evaluate efficacy of erlotinib loaded CSLPHNPs in A549 cells, a human lung adenocarcinoma cell line. Optimized erlotinib loaded CSLPHNPs were prepared with mean particle size of about 170nm, PDI<0.2, drug entrapment efficiency of about 66% with good serum and storage stability. The evaluation of in vitro cellular efficacy results indicated enhanced uptake and efficacy of erlotinib loaded CSLPHNPs compared to erlotinib solution in A549 cells. Therefore, CSLPHNPs could be a potential delivery system for erlotinib in the therapy of NSCLC.
核壳型脂质-聚合物杂化纳米粒（CSLPHNPs）已成为一种多功能药物递送平台。该递送系统将聚合物核的机械优势和磷脂壳的仿生优势整合到一个单一平台中。我们报道了由脂质单层壳和可生物降解聚合物核组成的CSLPHNPs的研发情况，用于递送厄洛替尼，一种临床上用于治疗非小细胞肺癌（NSCLC）的抗癌药物。采用先前报道的单步超声法，以聚己内酯（PCL）作为可生物降解聚合物核，以由氢化大豆磷脂酰胆碱（HSPC）和1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]（DSPE-PEG2000）组成的磷脂壳制备负载厄洛替尼的CSLPHNPs。对负载厄洛替尼的CSLPHNPs的物理化学性质进行了表征，包括平均粒径、多分散指数（PDI）、zeta电位、形态、热分析和红外光谱分析、载药量、体外药物释放、体外血清稳定性和储存稳定性。研究并优化了关键制剂和工艺变量对负载厄洛替尼的CSLPHNPs的两个关键质量属性（平均粒径和药物包封率）的影响。此外，进行了体外细胞摄取、发光细胞活力测定和集落形成测定，以评估负载厄洛替尼的CSLPHNPs在人肺腺癌细胞系A549细胞中的疗效。制备的优化负载厄洛替尼的CSLPHNPs平均粒径约为170nm，PDI<0.2，药物包封率约为66%，具有良好的血清和储存稳定性。体外细胞疗效结果评估表明，与厄洛替尼溶液相比，负载厄洛替尼的CSLPHNPs在A549细胞中的摄取和疗效增强。因此，CSLPHNPs可能是NSCLC治疗中厄洛替尼的一种潜在递送系统。
