Quality by Design Galvanized development of resveratrol loaded PLGA nanoparticles: In vitro and Ex vivo evaluation for the non-invasive treatment of metastatic melanoma

被引：6

作者：

Vambhurkar, Ganesh ^{[1
]}

Famta, Paras ^{[1
]}

Shah, Saurabh

Jain, Naitik

Srinivasarao, Dadi A. ^{[1
]}

Sharma, Anamika

Shahrukh, Syed ^{[1
]}

Khatri, Dharmendra Kumar

Singh, Shashi Bala ^{[2
]}

Srivastava, Saurabh ^{[1
,3
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmaceut, Pharmaceut Innovat & Translat Res Lab PITRL, Hyderabad, India

[2] Natl Inst Pharmaceut Educ & Res, Dept Biol Sci, Hyderabad, India

[3] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmaceut, Balanagar, Hyderabad 500037, Telangana, India

来源：

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY | 2024年 / 91卷

关键词：

Melanoma; Metastasis; PLGA-Nanoparticles; Resveratrol; CELLULAR UPTAKE; ADVERSE EVENTS; DRUG-DELIVERY; PATHWAY; HEAD;

D O I：

10.1016/j.jddst.2023.105252

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Melanoma is a lethal form of skin cancer, which progresses with poor prognosis. The melanoma tumors are highly metastatic in nature, which often leads to tumorigenesis in lungs and brain tissues. Invasion and migration are mainly responsible for poor 5-year survival rate of similar to 32 % after diagnosis of melanoma. The limitations of conventional melanoma therapy include insufficient drug accumulation in tumor due to distal nature of the tumor, and chemoresistance. Resveratrol (RES) is a TGF-beta and WNT/beta-catenin inhibitor reported to suppress cancer cell proliferation, invasion, and migration. Therefore, we developed RES-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (RES-PLGA-NPs), and embedded within the carbopol hydrogel to achieve site-specific delivery of resveratrol to melanoma cells. During development stage, we employed quality by design (QbD) approach to understand the process parameters. Consequently, we observed 1.26-fold reduction in IC50 for RES-PLGA-NPs compared to unformulated RES. Scratch assay demonstrated the ability of RES and RES-PLGA-NPs to inhibit the migratory properties of melanoma (B16-F10) cells. Further, cell cycle analysis demonstrated that RES and RES-PLGA-NPs arrested cell cycle progression in G2/M phase. Based on these studies we concluded that RES-PLGA-NPs offered enhanced therapeutic effect by inhibiting cell cycle progression, proliferation and invasion of metastatic melanoma cells. Therefore, delivery of RES via nanoparticulate delivery system may have immense potential for metastatic melanoma treatment.

引用

页数：11