Combination Drug Therapy using Biodegradable Thermosensitive Polymer PLGA-PEG-PLGA
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AbstractIntroduction: Drug combination can generally improve treatment efficacy by multiple molecular targeting. However, sustain drug delivery systems which can accommodate multiple drugs with low solubility still fall short. In this study, PLGA-PEG-PLGA loaded with two drugs, a tyrosine kinase inhibitor pazopanib (PZP) and corticosteroid dexamethasone (DEX), were used to investigate the drug loading and release profile. Ultimately, this formulation will be further investigated in an in-vivo model.

Methods: DEX and PZP were incorporated into 20% w/v PLGA-PEG-PLGA polymeric solution via physical mixing. After filtering through 0.22 m filter, the drug loaded polymeric solutions were analyzed for drug concentration. The release profiles of each formulation were monitored for 30 days once the polymeric solutions undergo sol-gel transition at 37 oC.

Results: Relative to their solubility in water, PLGA-PEG-PLGA at 20% w/v increased the solubility of DEX and PZP by 4.8x and 970x respectively. Compared with the single drug formulations, co-loading of the two drugs into PLGA-PEG-PLGA did not cause any appreciable change in their solubility. This phenomenon was also observed in 10% w/v polymer solutions.
Interestingly, the dual drug formulation exhibits sequential drug release as shown In Fig. 1 and Fig. 2. DEX came out first followed by PZP. This observation is attributable to the different physico-chemical properties of the two drugs, which renders the different locations of the two drugs in the gel. Based on the release profile, it is likely that DEX released out via diffusion but polymer degradation/erosion may account for the release of PZP. This is further supported by the independent release of the two drugs from the gel relative to the single drug formulations.

Conclusion: The release profiles of different drugs in PLGA-PEG-PLGA can be easily tuned by carefully selecting drugs with appropriate physico-chemical properties.
Acceptance Date16/07/2017
All Author(s) ListHo Yin LI, Pui Shan CHAN, Thomas Wai Yip LEE
Name of Conference2017 Annual Meeting - Controlled Release Society
Start Date of Conference16/07/2017
End Date of Conference19/07/2017
Place of ConferenceBoston
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

Last updated on 2018-18-01 at 08:33