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Abstract The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi‐synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline‐loaded poly(lactic‐co‐glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87‐MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87‐MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline‐loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies.
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Longer Acting Injectable: Continuous, Linear Release of a Progestin Contraceptive From an Oxidized Porous Silicon Host
Abstract Maintaining stable drug concentrations in the bloodstream is a challenge for injectable hydrophobic progestin contraceptives. This work investigates porous silicon dioxide (pSiO2) microparticles as a delivery vehicle for progestins via melt‐infiltration of drugs into the mesopores. The pSiO2is prepared through electrochemical anodization of single‐crystalline silicon followed by thermal oxidation, yielding vertically oriented pores (≈50 nm diameter) with porosity varied (between 35–75%) to optimize drug loading and release. Among the progestins tested, etonogestrel and levonorgestrel (LNG) decompose near their melting points, preventing melt infiltration. However, addition of 20% cholesterol by mass suppresses the melting point of LNG sufficiently to enable loading without degradation. Mass loadings exceeding 50% (drug: drug + carrier) are achieved for segesterone acetate (SEG) and LNG, retaining drug crystallinity as confirmed by X‐ray diffraction. In vitro, both SEG and LNG‐loaded pSiO2display sustained drug release for up to 3 months, with reduced burst release, more constant steady‐state concentrations, and a substantially reduced tail compared to pure LNG or SEG, or SEG loaded into pSiO2from a chloroform solution. In a pilot in vivo study, SEG‐loaded pSiO2microparticles are well tolerated in 20‐week‐old female rats over a 25‐week period, with no signs of toxicity.
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- Award ID(s):
- 2011924
- PAR ID:
- 10640278
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 14
- Issue:
- 26
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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