John Garner

Maleimide-PEG-PLGA from PolySciTech used in development of bladder cancer therapy

Blog Post created by John Garner on Aug 19, 2019

One treatment option for bladder cancer is delivery of chemotherapeutics directly into the bladder itself (Intravesical Therapy). Delivery of chemotherapeutics to bladder cancer tumors by this method is difficult due to the low permeability of the bladder, periodic voiding, and other limitations. Recently, researchers at University of Reading (United Kingdom), Al-Farabi Kazakh National University (Kazakhstan), Heinz Maier-Leibnitz Zentrum(Germany) and Harvard University used PLGA-PEG-Mal (AI020, AI109) from PolySciTech (www.polyscitech.com) to develop muco-adhesive nanoparticles. This research holds promise to provide for improved therapeutic strategies against bladder cancer. Read more: Kaldybekov, Daulet B., Sergey K. Filippov, Aurel Radulescu, and Vitaliy V. Khutoryanskiy. "Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery." European Journal of Pharmaceutics and Biopharmaceutics (2019). https://www.sciencedirect.com/science/article/abs/pii/S0939641119307258

“Abstract: Low permeability of the urinary bladder epithelium, poor retention of the chemotherapeutic agents due to dilution and periodic urine voiding as well as intermittent catheterisations are the major limitations of intravesical drug delivery used in the treatment of bladder cancer. In this work, maleimide-functionalised poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles were developed. Their physicochemical characteristics, including morphology, architecture and molecular parameters have been investigated by means of dynamic light scattering, transmission electron microscopy and small-angle neutron scattering techniques. It was established that the size of nanoparticles was dependent on the solvent used in their preparation and molecular weight of PEG, for example, 105 ± 1 nm and 68 ± 1 nm particles were formed from PLGA20K-PEG5K in dimethyl sulfoxide and acetone, respectively. PLGA-PEG-Mal nanoparticles were explored as mucoadhesive formulations for drug delivery to the urinary bladder. The retention of fluorescein-loaded nanoparticles on freshly excised lamb bladder mucosa in vitro was evaluated and assessed using a flow-through fluorescence technique and Wash Out50 (WO50) quantitative method. PLGA-PEG-Mal nanoparticles (NPs) exhibited greater retention on urinary bladder mucosa (WO50 = 15 mL) compared to maleimide-free NPs (WO50 = 5 mL). The assessment of the biocompatibility of PEG-Mal using the slug mucosal irritation test revealed that these materials are non-irritant to mucosal surfaces. Graphical abstract: Schematic illustration depicting the mechanism of enhanced mucoadhesion of PLGA-PEG-Mal nanoparticles on urinary bladder mucosa. Keywords: urinary bladder intravesical drug delivery PLGA-PEG maleimide nanoparticles small-angle neutron scattering slug mucosal irritation test muco-adhesion Wash Out50 (WO50)”

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