GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting

被引:21
|
作者
Jagdale, Saili [1 ]
Narwade, Mahavir [1 ]
Sheikh, Afsana [2 ]
Md, Shadab [3 ]
Salve, Rajesh [4 ,5 ]
Gajbhiye, Virendra [4 ,5 ]
Kesharwani, Prashant [2 ,6 ,7 ]
Gajbhiye, Kavita R. [1 ,8 ]
机构
[1] Poona Coll Pharm, Dept Pharmaceut, Bharati Vidyapeeth, Pune, India
[2] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut, New Delhi 110062, India
[3] King Abdulaziz Univ, Fac Pharm, Dept Pharmaceut, Jeddah 21589, Saudi Arabia
[4] Agharkar Res Inst, Nanobioscience Grp, Pune, India
[5] Savitribai Phule Pune Univ, Ganeshkhind, Pune 411007, India
[6] Saveetha Inst Med & Tech Sci, Saveetha Dent Coll, Ctr Transdisciplinary Res, Dept Pharmacol, Chennai 602105, India
[7] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut, New Delhi 110062, India
[8] Bharati Vidyapeeth Deemed Univ, Poona Coll Pharm, Dept Pharmaceut, Pune 411038, India
关键词
Ovarian cancer; Solid-lipid nanoparticles (SLN); Paclitaxel; GLUT1; N-acetyl-d-glucosamine (GLcNAc); Targeted drug delivery; PACLITAXEL; DELIVERY; CYTOTOXICITY; DOXORUBICIN; DENDRIMER;
D O I
10.1016/j.ijpharm.2023.122894
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nano-medicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distri-bution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.
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页数:11
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