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Cancer Chemistry

Abstract 1325: Oral delivery of drug-loaded microspheres for cancer

Duc P. Do
Duc P. Do
Chicago State University College of Pharmacy, Chicago, IL.
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DOI: 10.1158/1538-7445.AM2016-1325 Published July 2016
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Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA

Abstract

The oral route remains the preferred method of administering drugs; however, this delivery mode faces many challenges, including low bioavailability of the administered drug, generalized toxicity and drug decomposition. Microsphere drug delivery systems have evolved to improve patient compliance, reduce toxicity, and increase efficacy. Additionally, the use of microspheres to deliver drugs has many other advantages, such as control-release of the active drug, increase bioavailability and target delivery of the drug to the desired tissue/cell. Our research explored the utility of encapsulating vorinostat in biodegradable microsphere delivery system, to be delivered orally via a capsule, to attain effective therapeutic effect. The strategy is to develop an oral, biodegradable albumin-based microsphere delivery system containing vorinostat that would elicit targeted inhibitory effect on cancer to enhance therapeutic efficacy. Vorinostat-loaded microspheres were prepared by a microencapsulation method through spray drying. The parameters for spray drying were optimized to find the best formulation for enhanced uptake and efficacy in vitro in cultured HEPG2 cells. Microspheres were loaded into capsules. Microspheres and capsule formulations were assessed for particle size, particle size distribution, surface morphology and properties and Zeta potential measurements. Drug release characteristics were quantified using dissolution studies. Chemical and thermal stability of the encapsulated drug and microsphere formulations were evaluated using FTIR and DSC, respectively. The uptake and cellular internalization of the microspheres were evaluated using co-cultures of Caco-2 cells and Raji cells. In vitro cytotoxicity was evaluated using MTT and clonogenic assays. Histone deacetylase (HDAC) activity levels in cells from treatment of free vorinostat and microparticle formulation were compared. Global histone modifications in HEPG2 cancer cells due to vorinostat-loaded microsphere treatment were also analyzed. Our data indicated that vorinostat microspheres were 1-2 microns in size and possessed spherical morphology. Zeta potential measurements show values of -30 mV, which indicated colloidal stability of the microsphere dispersion. Uptake studies indicated that more than 50% of the microspheres were internalized inside the cells within 12 hours. Additionally, dissolution studies showed that within 24 hours, 80% of the drug is sustained-release from the microsphere formulations. HDAC activity levels were shown to be decreased in cultured cells when vorinostat microspheres were used. Our in vitro studies showed that drug-loaded microsphere formulations exert cytotoxic effects on cultured cells. In summary, microspheres were shown to be a potential effective oral delivery system to administer anticancer drugs, with enhanced efficacy due to their controlled-release manner.

Citation Format: Duc P. Do. Oral delivery of drug-loaded microspheres for cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1325.

  • ©2016 American Association for Cancer Research.
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Cancer Research: 76 (14 Supplement)
July 2016
Volume 76, Issue 14 Supplement
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Abstract 1325: Oral delivery of drug-loaded microspheres for cancer
Duc P. Do
Cancer Res July 15 2016 (76) (14 Supplement) 1325; DOI: 10.1158/1538-7445.AM2016-1325

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Abstract 1325: Oral delivery of drug-loaded microspheres for cancer
Duc P. Do
Cancer Res July 15 2016 (76) (14 Supplement) 1325; DOI: 10.1158/1538-7445.AM2016-1325
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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