Abstract
Schizophrenia and post-operative pain present significant clinical challenges due to poor medication adherence and opioid dependence risks. To address these issues, this thesis aims to develop novel, long-acting implantable drug delivery systems (IDDSs) utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) to effectively deliver the antipsychotic risperidone (RIS) and the local anaesthetic bupivacaine (BUP).Supported by validated HPLC-UV quantification, the research employed two distinct fabrication strategies. First, a minimally invasive in-situ forming implant (ISFI) system combined with 3D-printed hollow microneedles was developed for RIS. Second, a solvent-free Vacuum Compression Molding (VCM) technique was utilized to fabricate solid implants. All formulations underwent extensive physicochemical characterization to evaluate drug stability and matrix integrity.
Optimization of the RIS ISFI yielded minimal burst release and an ideal cumulative profile, with microneedles demonstrating reliable skin penetration. For VCM solid implants, polymer molecular weight significantly governed RIS release kinetics, enabling prolonged delivery. Additionally, an engineered VCM bilayer BUP implant successfully achieved a dual-release profile for perioperative pain, combining a rapid onset layer with a dense core for sustained maintenance.
Ultimately, these versatile, fully biodegradable PLGA systems offer tunable release profiles and eliminate the need for surgical removal. Moving forward, they present promising, patient-friendly therapeutic alternatives capable of improving treatment compliance, reducing opioid reliance, and revolutionizing the long-term management of psychiatric conditions and acute pain.
Thesis is embargoed until 31 July 2031.
| Date of Award | Jul 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Eneko Larrañeta (Supervisor) & Ryan Donnelly (Supervisor) |
Keywords
- Implant
- IDDSs
- ISFI
- VCM
- Risperidone
- Bupivacaine
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