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Title: Formulation and Evaluation of Ligand Appended Lipid Nanoparticulate Systems for Oral Delivery of Anti Cancer Agents
Researcher: Khatri, Hiren
Guide(s): Patel, Mayur
Keywords: Clinical Pre Clinical and Health
lipid nanoparticles
University: Nirma University
Completed Date: 2019
Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. Toxicity of anticancer drugs towards normal cells is one of the major concern hampering the effective chemotherapy. Artemether (ART) has been reported to possess anticancer activity and able to enhance anticancer potential of chemotherapy drugs. The oral bioavailability of paclitaxel (PTX), which is an effective drug in NSCLC, is limited due to being a substrate of P-glycoprotein (P-gp), multidrug ef and#64258;ux transporter in the intestine. Marketed preparations of PTX are associated with numerous dose related toxicities. The aim of present investigation is to develop folate appended PEGylated solid lipid nanoparticles (SLNs) of PTX (FPS) and ART (FAS). MTT assays revealed better cytotoxicity of FPS when given in combination with FAS on human lung cancer cell line H-1299, as compared to pure drugs, unconjugated SLNs and FPS alone. The cellular uptake of FPS and FAS was confirmed by fluorescence imaging and flow cytometric analysis. In vivo pharmacokinetic study revealed better absorption and long circulation of FPS and FAS, which further leads to increased relative bioavailability of drugs (13.81 folds and 7.07 folds for PTX and ART, respectively) as compared to their solutions counterpart. In vivo pharmacodynamic study confirmed tumor regression of developed SLNs formulations, which was observed highest when used in combination of FPS and FAS. Serum creatinine, blood urea nitrogen (BUN), SGOT, albumin and total protein levels revealed that formulated FPS and FAS do not exhibit any renal and hepatic toxicity. Additionally, novel formulation H1 of PTX (H1P) and of ART (H1A) was developed, the combination of which has been proved to be better than the combination of formulations FPS and FAS. Thus, it can be concluded that by administering ART as SLNs formulation along with PTX as SLNs via oral route, anticancer potential of PTX was improved without any toxicity (both renal and hepatic), which indicate the ability
Appears in Departments:Institute of Pharmacy

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10. chapter 1.pdfAttached File454.44 kBAdobe PDFView/Open
11. chapter 2.pdf220.86 kBAdobe PDFView/Open
12. chapter 3.pdf693.46 kBAdobe PDFView/Open
13. chapter 4.pdf738 kBAdobe PDFView/Open
14. chapter 5.pdf915.38 kBAdobe PDFView/Open
15. bibliography.pdf49.5 kBAdobe PDFView/Open
16. summary.pdf31.94 kBAdobe PDFView/Open
17. conclusion.pdf31.94 kBAdobe PDFView/Open
1. title.pdf59.07 kBAdobe PDFView/Open
2. certificate.pdf61.25 kBAdobe PDFView/Open
3. declaration.pdf72.43 kBAdobe PDFView/Open
4. ackowledgement.pdf58.55 kBAdobe PDFView/Open
5. abstract.pdf63.34 kBAdobe PDFView/Open
6. content.pdf30.03 kBAdobe PDFView/Open
7. abbreviations.pdf56.51 kBAdobe PDFView/Open
80_recommendation.pdf99 kBAdobe PDFView/Open
8. list of figures.pdf37.89 kBAdobe PDFView/Open
9. list of tables.pdf27.9 kBAdobe PDFView/Open
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