Development of polymeric nanoparticles for intravesical drug delivery to the bladder

Lazauskaite, Sandra (2024) Development of polymeric nanoparticles for intravesical drug delivery to the bladder. Doctoral thesis, University of East Anglia.

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Abstract

Urinary tract infections (UTIs) are one of the most commonly acquired bacterial infections, resulting in frequent hospitalisations and increased economic burden on the healthcare system. Due to the systemic exposure during the treatment, UTIs are often associated with increased risk of side effects, diminished therapeutical effects within the bladder, and increased risk of uropathogenic bacteria acquiring antimicrobial resistance.

Intravesical drug delivery (IDD) to the bladder was proposed as a solution for improved drug delivery. IDD ensures full drug dosage instillation into the infection site, reduces systemic exposure due to poor permeability of the bladder, and minimises the risk of side effects. However, IDD suffers from fast drug dilution and wash-out, due to bladder physiological functions such as urine filling and voiding. Therefore, use of nanotechnology has been proposed, as coupled with mucoadhesive materials, drug nanocarriers would attach to the bladder lining, prolonging drug retention time in the bladder. Additionally, drug entrapment into polymeric nanoparticles could reduce drug associated toxicity and demonstrate sustained drug release.

The aim of this project is to obtain two types of colloidally stable drug loaded polymeric nanoparticles and enhance their mucoadhesive properties for prolonged retention time in the bladder. The work presented herein involves the preparation, optimisation and characterisation of hydrophilic antibiotic loaded and hydrophobic cyclooxygenase-2 inhibitor drug loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Comparison between nanoparticle synthesis methods was performed by utilising Design of Experiments, studying how nanoparticle preparation parameters affect the physicochemical characteristics of drug loaded PLGA nanoparticles. Additionally, chitosan was incorporated into nanoparticle formulations, resulting in particles exhibiting cationic charge, allowing them to form electrostatic interactions with anionic mucin layer of the urothelium. Finally, to improve the entrapment of hydrophilic drugs into PLGA nanoparticles, hydrophobic ion pairing technique was used to increase hydrophobicity of the antibiotic, also sustaining its drug release rate.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
Depositing User:	Chris White
Date Deposited:	03 Apr 2025 10:22
Last Modified:	03 Apr 2025 10:22
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98925
DOI:

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