Cardoso Maria Margarida, Peça Inês N, Bicho Ana
LAQV-REQUIMTE, Departamento de Química, Nova School of Science and Technology (NOVA FCT), Universidade NOVA de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal.
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Materials (Basel). 2024 Jul 17;17(14):3544. doi: 10.3390/ma17143544.
Nanoparticles (NPs) have become attractive vehicles for drug delivery in cancer therapy due to their ability to accumulate in tumours and mitigate side effects. This study focuses on the production of doxorubicin (DOX)-loaded NPs comprising Poly (lactic-co-glycolic acid)-Polyethylene glycol with varying PEG proportions and the examination of their impact on drug release kinetics. DOX-loaded NPs, composed of PLGA-co-PEG with PEG contents of 0%, 5%, 10%, and 15%, were synthesized by the solvent evaporation technique, exhibited spherical morphology, and had sizes ranging from 420 nm to 690 nm. In vitro drug release studies revealed biphasic profiles, with higher PEG contents leading to faster and more extensive drug release. The Baker-Lonsdale model demonstrated the best fit to the drug release data, indicating that the release process is diffusion-controlled. The diffusion coefficients for DOX determined ranged from 6.3 × 10 to 7.55 × 10 cms and exhibited an upward trend with increasing PEG content in the polymer. In vitro cytotoxicity tests with CHO cells showed that unloaded NPs are non-toxic, while DOX-loaded PLGA-PEG 15% NPs induced a greater decrease in cellular viability compared to their PLGA counterparts. A mathematical relationship between the diffusion coefficient and PEG percentage was derived, providing a practical tool for optimizing DOX release profiles.
纳米颗粒(NPs)因其能够在肿瘤中聚集并减轻副作用,已成为癌症治疗中颇具吸引力的药物递送载体。本研究聚焦于制备负载阿霉素(DOX)的纳米颗粒,其由聚(乳酸 - 乙醇酸)-聚乙二醇组成,聚乙二醇比例各异,并考察它们对药物释放动力学的影响。通过溶剂蒸发技术合成了负载DOX的纳米颗粒,其由PEG含量分别为0%、5%、10%和15%的PLGA - co - PEG组成,呈现球形形态,尺寸范围为420纳米至690纳米。体外药物释放研究显示出双相特征,PEG含量越高,药物释放越快且越充分。Baker - Lonsdale模型对药物释放数据拟合最佳,表明释放过程受扩散控制。所测定的DOX扩散系数范围为6.3×10至7.55×10厘米²/秒,且随聚合物中PEG含量的增加呈上升趋势。用CHO细胞进行的体外细胞毒性试验表明,未负载的纳米颗粒无毒,而负载DOX的15% PLGA - PEG纳米颗粒相比其PLGA对应物诱导细胞活力有更大程度的降低。推导了扩散系数与PEG百分比之间的数学关系,为优化DOX释放曲线提供了实用工具。