In vitro evaluations of bisphosphonate therapy in refractory cancer by targeting tumor-associated macrophages

Permanent URL: http://hdl.handle.net/2047/d20004932
Title:
In vitro evaluations of bisphosphonate therapy in refractory cancer by targeting tumor-associated macrophages
Creator:
Doshi, Aatman S. (Author)
Contributor:
Amiji, Mansoor M. (Advisor)
Amiji, Mansoor M. (Committee member)
Zhenfeng, Duan (Committee member)
Gatley, Samuel (Committee member)
Publisher:
Boston, Massachusetts : Northeastern University, 2013
Date Accepted:
August 2013
Date Awarded:
January 2014
Type of resource:
Text
Genre:
Masters theses
Format:
electronic
Digital origin:
born digital
Abstract/Description:
The main aim of this MS thesis project was to develop a targeted drug delivery system which is capable of targeting tumor-associated macrophages (TAMs). Alendronate sodium trihydrate which is a bisphosphonate drug which is originally a drug used for osteoporosis, was repurposed for its ability to kill TAMs. Non-targeted liposomal formulation was developed using a film hydration method, which was able to encapsulate alendronate sodium trihydrate. Lyp-1 was selected as a targeting peptide which has a capability to bind to p32/hyaluronic acid binding receptor/gC1qR/p33 expressed highly on tumor cells and TAM's. Lyp-1-modified liposomes were synthesized to encapsulate alendronate sodium trihydrate. Both, qualitative and quantitative in vitro cell uptake studies were performed in J774.A1 murine macrophages, using these formulations. Qualitative cell uptake studies showed preferential uptake by targeted liposomal formulation, while quantitative studies did not show any difference in uptake by the macrophages showing the non-specific phagocytic nature of the macrophages. The formulations were further tested in vitro for their cytotoxicity profile. It was found that the Lyp-1 modified liposomes were more efficient in killing cells in comparison to non-targeted liposomes and free drug. Apoptosis studies were performed and both the formulations (non-targeted and targeted liposomes) and free drug induced cell death in the macrophages by necrosis.
Subjects and keywords:
Anti-cancer
Formulations
In vitro assays
Liposomes
Pharmaceutics and Drug Design
Pharmacy and Pharmaceutical Sciences
DOI:
https://doi.org/10.17760/d20004932
Permanent Link:
http://hdl.handle.net/2047/d20004932
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