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Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery
Daulet B Kaldybekov1, Sergey K Filippov2, Aurel Radulescu3
1School of Pharmacy, University of Reading, Whiteknights, RG6 6AD Reading, United Kingdom; Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, 050040 Almaty, Kazakhstan.
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.
Insights
New mucoadhesive nanoparticles improve intravesical drug delivery for bladder cancer. Poly(lactide-co-glycolide)-block-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) nanoparticles show enhanced retention on bladder tissue, overcoming key limitations of current treatments.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Intravesical chemotherapy for bladder cancer faces limitations like poor drug retention and epithelial permeability.
- Developing effective drug delivery systems is crucial to enhance treatment efficacy and reduce systemic side effects.
Purpose of the Study:
- To develop and characterize maleimide-functionalized poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles for enhanced mucoadhesive drug delivery to the urinary bladder.
- To evaluate the in vitro retention and biocompatibility of these novel nanoparticles.
Main Methods:
- Nanoparticles were synthesized and characterized using dynamic light scattering, transmission electron microscopy, and small-angle neutron scattering.
- Mucoadhesion and retention were assessed using a flow-through fluorescence technique and the Wash Out50 (WO50) method on excised lamb bladder mucosa.
- Biocompatibility was evaluated using the slug mucosal irritation test.
Main Results:
- PLGA-PEG-Mal nanoparticle size was influenced by solvent and PEG molecular weight.
- Maleimide-functionalized nanoparticles demonstrated significantly greater retention on bladder mucosa (WO50 = 15 mL) compared to maleimide-free nanoparticles (WO50 = 5 mL).
- PEG-Mal materials exhibited non-irritant properties in the slug mucosal irritation test.
Conclusions:
- PLGA-PEG-Mal nanoparticles represent a promising mucoadhesive formulation for improving intravesical drug delivery in bladder cancer treatment.
- These nanoparticles effectively enhance drug retention within the urinary bladder, addressing a key challenge in current therapies.
- The developed nanoparticles are biocompatible and non-irritant, suggesting their potential for safe clinical application.
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