Alkholief Musaed, Kalam Mohd Abul, Anwer Md Khalid, Alshamsan Aws
Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Pharmaceutics. 2022 Apr 15;14(4):870. doi: 10.3390/pharmaceutics14040870.
A biocompatible, biodegradable and FDA-approved polymer [Poly lactic--glycolic acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of solvents, stabilizers and their concentrations on the physical properties of the PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects of different proportions of PVA/PVP with DCM/chloroform on the physiochemical properties (particle size, the polydispersity index, the zeta potential by Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was used to check the physical state, the possible complexation of PLGA with stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. Average size of 273.2-563.9 nm was obtained when PVA (stabilizer) with DCM, whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 273.2-563.9 nm when PVP was the stabilizer with DCM, while it was 381.4-466.6 nm with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative (-0.62 mV) while they were comparatively higher and positive for PVP-stabilized NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1-3%), which resulted in sufficient encapsulation (54.94-74.86%) and drug loading (4.99-6.81%). No endothermic peak of PVA/PVP appeared in the optimized formulation, which indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro release study indicated a sustained release of IND (32.83-52.16%) from the PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics followed by Korsmeyer-Peppas models. The cell proliferation assay clearly established that the organic solvents used to prepare PLGA-NPs had evaporated. The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the dose range of IND (250-500 µg/mL) and at an equivalent concentration of PLGA-NPs (3571.4-7142.7 µg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced by its encapsulation into PLGA-NPs. The outcomes of this investigation could be implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of low/high molecular weight drugs. It would be useful for further in vitro and in vivo applications to use this delivery system.
一种具有生物相容性、可生物降解且经美国食品药品监督管理局（FDA）批准的聚合物[聚乳酸-乙醇酸共聚物（PLGA）]被用于制备纳米颗粒（NPs），以观察溶剂、稳定剂及其浓度对PLGA-NPs物理性质的影响，随后进行吲哚美辛（IND）的包封和体外释放。采用单乳液溶剂蒸发技术，以二氯甲烷（DCM）/氯仿为有机相，聚乙烯醇（PVA）/聚乙烯吡咯烷酮（PVP）为稳定剂来制备包封IND的PLGA-NPs。研究了不同比例的PVA/PVP与DCM/氯仿对NPs物理化学性质（粒径、多分散指数、通过马尔文粒度分析仪测定的zeta电位以及通过扫描电子显微镜观察的形态）的影响。差示扫描量热法（DSC）用于检查物理状态、PLGA与稳定剂可能的络合情况以及包封药物的结晶度。所有浓度的稳定剂均产生球形、形状规则、表面光滑的离散NPs。当PVA（稳定剂）与DCM混合时，平均粒径为273.2 - 563.9 nm，而与氯仿混合时，粒径范围为317.6至588.1 nm。当PVP为稳定剂且与DCM混合时，粒径为273.2 -
