Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide‐loaded PLGA microparticles for the treatment of glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ‐loaded poly(lactic‐co‐glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U‐87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ‐loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317–2324, 2019.

Design, Synthesis, and Biological Evaluation of Dexamethasone–Salvianolic Acid B Conjugates and Nanodrug Delivery against Cisplatin-Induced Hearing Loss

“…The release profile showed an initial burst release during the first 6 h with approximately 50% of encapsulated conjugate 1 or 2 being released from conjugate NPs. Subsequently, the rate of conjugate release decreased and reached 77% at 24 h. At the end of the 4 day release study, the drugs released plateaued at ∼80% for both NPs, which was consistent with the release profile of other typical NPs …”

“…In addition, the particle size and PDI of NPs in the PBS containing 10% FBS exhibited no obvious change (Figure At the end of the 4 day release study, the drugs released plateaued at ∼80% for both NPs, which was consistent with the release profile of other typical NPs. 46 Anti−ototoxicity Assay. The protective effects of the conjugates and NPs against CDDP-induced ototoxicity were examined using the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell model.…”

Long-Term Sustained Drug Delivery via 3D Printed Masks for the Development of a Heparin-Loaded Interlayer in Vascular Tissue Engineering Applications

“…Heparin-Loaded GelMA Application. dECM samples were secured on wooden frames and dehydrated with serial ethanol washes (20,40,60, 80, and 100%) for 5 min each with 3 additional 100% ethanol baths for 5 min each and then allowed to air-dry. 15 wt % gelMA was prepared in PBS with a heparin concentration of 50 mg/mL and added to the dehydrated dECM.…”

“…Surface treatments can be eluting or noneluting and work by way of discouraging platelet adhesion, , encouraging endothelial cell attachment, , or both. − However, eluting treatments typically provide only a short-term burst release, and much of the bioactive molecule is washed away, while noneluting approaches provide localized delivery, but treatment techniques can alter graft properties. ,− Encapsulation in microparticles and incorporation in electrospun fibers have been successful for extending drug release. However, the solvents used in these methods can be harsh and impair loading efficiency, release kinetics, and bioactivity. , Alternatively, gelatin methacrylate (gelMA) has been employed to achieve long-term sustained drug release without solvents and its properties can be influenced through UV crosslinking without any impairment to cell viability. − …”

“…However, the solvents used in these methods can be harsh and impair loading efficiency, release kinetics, and bioactivity. 20,21 Alternatively, gelatin methacrylate (gelMA) has been employed to achieve long-term sustained drug release without solvents and its properties can be influenced through UV crosslinking without any impairment to cell viability. 22−26 One drug commonly incorporated in vascular grafts to impede thrombosis is heparin.…”