Date of Award

2021

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences (Ph.D.)

Department

Pharmaceutical Sciences

First Advisor

Senshang Lin

Second Advisor

Bhagwan D Rohera

Third Advisor

Zhe-Sheng Chen

Abstract

Primary brain cancer cells grow within the brain or cancer cells can metastasis from different site of the body into brain. The major hurdle in the treatment of brain cancer is the presence of blood-brain barrier (BBB). Additionally, acquired multidrug-resistant (MDR) impedes the success of long-term chemotherapy. Therefore, the objective of this investigation is to evaluate the brain targeting potential of orally administered poly(butyl cyanoacrylate) nanoparticulate delivery systems (PBCA-NPDS), double-coated with Tween 80 and polyethylene glycol (PEG) 20000 for brain delivery of doxorubicin, that does not cross the BBB by itself. And, evaluate the MDR reversal potential of PBCA-NPDS. Doxorubicin-loaded PBCA-NPDS were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 in varied concentrations. Brain uptake study of double-coated doxorubicin-loaded PBCA-NPDS using bEnd.3 cell line suggested the role of clathrin-mediated endocytosis in the uptake of double coated doxorubicin-loaded PBCA-NPDS. When Transwell® permeable supports were used, significant transport of doxorubicin across the cell monolayer was observed by the double-coated formulations, in comparison to doxorubicin solution (p

Share

COinS