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Development and characterization of imatinib-loaded PEG-ASA polymeric micelles and co-administration with doxorubicin-loaded micelles.

Pardeshi, Apurva Rajesh (2021) Development and characterization of imatinib-loaded PEG-ASA polymeric micelles and co-administration with doxorubicin-loaded micelles. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Imatinib is a tyrosine kinase inhibitor widely used in the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Monotherapy with imatinib (IMA) can lead to resistance, toxicity, and related side effects. Using polymeric micelles to facilitate its targeted delivery to tumor tissues reduces systemic toxicity and helps to reduce rapid metabolism and renal clearance along with increasing drug accumulation in tumor tissue due to enhanced permeation and retention effect. COX2 plays a role in tumor cell proliferation, angiogenesis, inhibition of apoptosis, and immunosuppression. Its inhibition can thus lead to increased anti-tumor activity. 5-ASA is a known anti-inflammatory COX2 inhibitor and can be conjugated with a polymer to form a prodrug-based micellar carrier to load other chemotherapeutic agents. PEG-ASA polymer (PASA) was hence synthesized and used to load imatinib to form polymeric micelles. These micelles were then characterized for their size, morphology, as well as in vitro and in vivo anti-tumor efficacy. We further developed doxorubicin (DOX)-loaded PASA micelles and tested their combination effect with co-administration of imatinib-loaded PASA micelles.
Our studies demonstrated that combination of IMA- and DOX-loaded micelles showed a favorable anti-tumor efficacy in in vitro as well as in vivo studies and may represent a promising therapeutic strategy that warrants more studies in the future.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pardeshi, Apurva Rajeshapp42@pitt.eduapp42
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorLi, Songsol4@pitt.edu
Committee MemberMa, XiaochaoMXIAOCHA@pitt.edu
Committee MemberSun, Jingjingjis84@pitt.edu
Date: 16 April 2021
Date Type: Publication
Defense Date: 30 March 2021
Approval Date: 16 April 2021
Submission Date: 16 April 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 42
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Imatinib, Polymeric micelle, Chemotherapeutic Nanoparticle, Doxorubicin, COX 2, Tumor microenvironment
Date Deposited: 16 Apr 2021 16:54
Last Modified: 16 Apr 2021 16:54
URI: http://d-scholarship.pitt.edu/id/eprint/40642

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