In this work, PLGA scaffolds with different architectures were fabricated to investigate the effects of surface area to volume ratio (SVR) (which resulted from the different architectures) on scaffold degradation characteristics and drug release kinetics with minocycline as the model drug. It was hypothesized that the thin strand scaffolds, which had the highest SVR, would degrade faster than the thick strand and globular scaffolds as the increase in surface area will allow more contact between water molecules and degradable ester groups in the polymer. However, it was found that globular scaffolds, which had the lowest SVR, resulted in the fastest degradation which demonstrated that the amount of degradation of the scaffolds does not only depend on the SVR but also on other factors such as the retention of acidic degradation byproducts in the scaffold and scaffold porosity. PLGA 50 : 50 globular scaffolds resulted in a biphasic release profile, with a burst release in the beginning and the middle of the release study which may be beneficial for some drug delivery applications. A clear correlation between SVR and release rates was not observed, indicating that besides the availability of more surface area for drug to diffuse out of the polymer matrix, other factors such as amount of scaffold degradation and scaffold porosity may play a role in determining drug release kinetics. Further studies, such as scanning electron microscopy, need to be performed in the future to further evaluate the porosity, morphology and structure of the scaffolds.

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Minocycline is a tetracycline derivative that was originally used clinically as an antibiotic and is currently being investigated as an anti-angiogenic factor for the treatment of different cancers including intracranial tumors such as glioblastomas. Due to its lipophilic nature, it has difficulty dissolving completely in organic or aqueous solvents and thus, presents a challenge for the fabrication of these particles via the emulsion-solvent evaporation method. The aim of this study is to investigate the effects of different methods of fabricating minocycline loaded microparticles on particle properties, such as the diameter, drug loading and release kinetics of the microparticles. Microparticles loaded with drug during the fabrication process were produced via two different methods: 1) an oil-in-water (O/W) single emulsion-solvent evaporation method where the drug was dissolved in the oil phase (denoted as “O/W particles”) and 2) a water-in-oil-in-water (W/O/W) double emulsion-solvent evaporation method where the drug was dissolved in the first water phase (denoted as “W/O/W particles”). Empty microparticles were also fabricated by a W/O/W method and loaded with drug after fabrication by dripping a drug solution onto freeze dried particles which were then left overnight at 4°C to allow the drug to adsorb onto and absorb into the particles (denoted as “prefabricated particles”). Light microscopy images of the particles were obtained and used to measure the diameters of the particles with the ImageJ software. The drug loading and release kinetics were determined by measuring the absorbance of minocycline at 350 nm with a microplate reader. The prefabricated particles resulted in larger diameters compared to the O/W and W/O/W particles which were loaded during the fabrication process. This could have resulted from the use of a vortex instead of a homogenizer/sonicator for the prefabricated scaffold which produces an emulsion with a lower speed compared to a homogenizer/sonicator. The prefabricated particles had a higher amount of drug loaded compared to O/W and W/O/W particles which were loaded during the fabrication process. By loading the drug after fabricating the particles, almost all of the drug can be adsorbed onto and/or absorbed into the particles without resulting in much loss of the drug. Alternatively, by loading the particles during the fabrication process, a lot of drug is lost into the water and/or oil phase and thus reducing the loading efficiencies of the particles. However, the particles loaded during the fabrication process were able to prolong the release of the loaded drug compared to the prefabricated scaffold which lost almost all of its drug by Day 1. In conclusion, although the prefabricated particles allow for the complete loading of the drug, the particles loaded during the fabrication process are more promising as controlled release vehicles as they are able to better sustain the release of the loaded drug. Citation Format: Sue Anne Chew, Marco Arriaga, Jesus R. Franco, Daniela Barbosa, Victor A. Hinojosa, Jose-Carlos Martinez, Paul Lenz. Fabrication of minocycline loaded PLGA microparticles for the treatment of intracranial tumors. [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 1366.