Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery

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.

Engineering the drug carrier biointerface to overcome biological barriers to drug delivery

“…PLGA-PEG components can be mixed with filler PLGA polymers to create PLGA particles with PEG decorated on the surface through the phase separation of hydrophilic PEG from hydrophobic PLGA. [44][45][46][47] This strategy have been used to improve systemic circulation time of carriers owing to decreased immunogenicity due to the protection offered by PEGylation. This method also works well with self-assembling systems, whereby different monomers can be mixed together in varying concentrations to decorate the surface of drug carriers with functional chemical handles, or to change the material surface properties such as charge or hydrophobicity.…”

Drug Delivery Systems of Natural Products in Oncology

“…Polymers utilized for nanoparticles of synthetic origin production are totally artificial, such as PLGA, PLA (Poly-lactic acid) and PMA (thiolated poly (methacrylic acid) [ 74 , 75 ]. Among these polymeric NPs, PLA-based nanoparticles showed a good potential in anticancer therapy.…”

Activity of Povidone in Recent Biomedical Applications with Emphasis on Micro- and Nano Drug Delivery Systems

“…In addition to these compounds, the synthetic polymers were also used. They include poly(N-isopropylacrylamide) [ 23 , 24 ], poly(acrylic acid) [ 25 , 26 ], poly(N-vinylcaprolactam) [ 27 , 28 ], polyethylene glycol [ 29 , 30 ], polyurethane [ 31 , 32 ] and some more.…”