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postgraduate thesis: Oleanolic acid delivery using biodegradable nanoparticles for cancer therapy

TitleOleanolic acid delivery using biodegradable nanoparticles for cancer therapy
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Man, K. D. [文冠慧]. (2015). Oleanolic acid delivery using biodegradable nanoparticles for cancer therapy. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388008
AbstractUtilization of nanocarriers is having a significant impact on the diagnosis and treatment of cancer. It allows targeted administration to specific sites and sustained drug delivery. Therefore, this regimen greatly increases the therapeutic index and drug concentration in tumor tissues. Among all types, biomaterials-based nanocarriers, owing to their biocompatible nature, offers a potentially safer strategy to improve the survival of cancer patients. This thesis investigated the therapeutic activity of copolymeric nanoparticulate systems encapsulated with oleanolic acid (OA). Four types of biodegradable copolymers, namely, mPEG-P(D,L)LA, mPEG-P(L)LA, mPEG-P(D,L)LGA and mPEG-P(L)LGA, were employed to fabricate OA-loaded nanoparticles (OA-NPs) by nanoprecipitation. Physicochemical characterizations were performed using dynamic light scattering (DLS), transmission electron microscope(TEM)and high performance liquid chromatography (HPLC). Cytotoxicity of the formulations was evaluated on A549 (human alveolar carcinoma), HepG2 (human liver carcinoma) and BEAS-2B (normal bronchial epithelial) cells via 3-(4, 5-dimethylthiazolyl-2)-2, 5- diphenyltetrazolium bromide (MTT) assay. The induced cell death pathway was confirmed by fluorescence-activated cellsorting (FACS) flow cytometry. The synthesized NPs were spherical, with size dimensions of 40-70nm. The particle size increased to 230-260nm after the incorporation of OA. Polydispersity indices of less than 0.3 indicated the narrow size distribution of the negatively charged NPs. OA-NPs in suspension form were stable over 7 days of storage atboth in 4°Cand 25°C. Significant inhibitory effect was demonstrated by the OA-NPs on A549 and HepG2 cell lines through apoptosis (p<0.05). In particular, OA-loaded mPEG-P(D,L)LGANPs were shown to be the most promising system suppressing over half of the A549 cell growth at OA concentration of 100ug/ml after 24 h and 72 h exposure. The corresponding toxic concentration on HepG2 cells was 40µg/ml. The anti-tumorefficacy of the OA-loaded systems followed the trend mPEG-P(D,L)LGA > mPEG-P(L)LGA > mPEG-P(D,L)LA > mPEG-P(L)LA NPs in decreasing order. The cytotoxic effect of OA-NPs on BEAS-2B cells was less than that on the two other cancer cell lines, while blank NPs (without OA incorporated) exhibited insignificant toxicity on all cell lines. This reflectedthe cytotoxic effect was ascribed to the encapsulated OA rather than the copolymeric NPs. Overall, our studies clearly revealed the specific anti-tumor capability of the developed OA-loaded nanoparticulate systems.
DegreeMaster of Philosophy
SubjectNanoparticles
Drug carriers (Pharmacy)
Cancer - Treatment
Dept/ProgramPharmacology and Pharmacy
Persistent Identifierhttp://hdl.handle.net/10722/222772

 

DC FieldValueLanguage
dc.contributor.authorMan, Kwun-wai, Dede-
dc.contributor.author文冠慧-
dc.date.accessioned2016-01-22T23:12:33Z-
dc.date.available2016-01-22T23:12:33Z-
dc.date.issued2015-
dc.identifier.citationMan, K. D. [文冠慧]. (2015). Oleanolic acid delivery using biodegradable nanoparticles for cancer therapy. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388008-
dc.identifier.urihttp://hdl.handle.net/10722/222772-
dc.description.abstractUtilization of nanocarriers is having a significant impact on the diagnosis and treatment of cancer. It allows targeted administration to specific sites and sustained drug delivery. Therefore, this regimen greatly increases the therapeutic index and drug concentration in tumor tissues. Among all types, biomaterials-based nanocarriers, owing to their biocompatible nature, offers a potentially safer strategy to improve the survival of cancer patients. This thesis investigated the therapeutic activity of copolymeric nanoparticulate systems encapsulated with oleanolic acid (OA). Four types of biodegradable copolymers, namely, mPEG-P(D,L)LA, mPEG-P(L)LA, mPEG-P(D,L)LGA and mPEG-P(L)LGA, were employed to fabricate OA-loaded nanoparticles (OA-NPs) by nanoprecipitation. Physicochemical characterizations were performed using dynamic light scattering (DLS), transmission electron microscope(TEM)and high performance liquid chromatography (HPLC). Cytotoxicity of the formulations was evaluated on A549 (human alveolar carcinoma), HepG2 (human liver carcinoma) and BEAS-2B (normal bronchial epithelial) cells via 3-(4, 5-dimethylthiazolyl-2)-2, 5- diphenyltetrazolium bromide (MTT) assay. The induced cell death pathway was confirmed by fluorescence-activated cellsorting (FACS) flow cytometry. The synthesized NPs were spherical, with size dimensions of 40-70nm. The particle size increased to 230-260nm after the incorporation of OA. Polydispersity indices of less than 0.3 indicated the narrow size distribution of the negatively charged NPs. OA-NPs in suspension form were stable over 7 days of storage atboth in 4°Cand 25°C. Significant inhibitory effect was demonstrated by the OA-NPs on A549 and HepG2 cell lines through apoptosis (p<0.05). In particular, OA-loaded mPEG-P(D,L)LGANPs were shown to be the most promising system suppressing over half of the A549 cell growth at OA concentration of 100ug/ml after 24 h and 72 h exposure. The corresponding toxic concentration on HepG2 cells was 40µg/ml. The anti-tumorefficacy of the OA-loaded systems followed the trend mPEG-P(D,L)LGA > mPEG-P(L)LGA > mPEG-P(D,L)LA > mPEG-P(L)LA NPs in decreasing order. The cytotoxic effect of OA-NPs on BEAS-2B cells was less than that on the two other cancer cell lines, while blank NPs (without OA incorporated) exhibited insignificant toxicity on all cell lines. This reflectedthe cytotoxic effect was ascribed to the encapsulated OA rather than the copolymeric NPs. Overall, our studies clearly revealed the specific anti-tumor capability of the developed OA-loaded nanoparticulate systems.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshNanoparticles-
dc.subject.lcshDrug carriers (Pharmacy)-
dc.subject.lcshCancer - Treatment-
dc.titleOleanolic acid delivery using biodegradable nanoparticles for cancer therapy-
dc.typePG_Thesis-
dc.identifier.hkulb5388008-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePharmacology and Pharmacy-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5388008-

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