Hydroxypropylmethacrylamide based thermoresponsive magnetomicelles for controllable drug delivery in pancreatic cancer

Alsuraifi, Ali Taha Yassen

Abstract

Thermo-responsive polymers are a class of smart polymers that respond to change in temperature. This property makes this type of polymers useful materials in a wide range of applications especially, in the field of drug delivery system. Polymers, which have primary amino groups, such as N-(3-aminopropyl) methacrylamide hydrochloride (APMA), have been used for post-polymerization modification reactions for the development of new materials for biomedical applications. Here I aim to fabricate an amphiphilic monomers composed of APMA by substituting (palmitoyl, dansyl, cholesteryl and oxadiazole) groups onto the primary amine in the APMA monomer.
These monomers were then copolymerized with N-(2-hydroxypropyl)methacrylamide (HPMA) in six different monomer feed ratios in order to characterise the effect of hydrophobic pendants on the copolymer properties including lower critical solution temperature (LCST), solubility, drug loading and drug release.

In this study drug loading and release properties of HPMA-co-APMA copolymers were studied by using four model hydrophobic drugs, propofol, griseofulvin, prednisolone and paclitaxel. High performance liquid chromatography (HPLC) measurements were performed in order to compare drug loading properties of the copolymer formulas. The most potent carrier candidate was loaded in order to carry out thermo-responsive release study. The results showed that all the copolymer formulations in this study possessed the ability to encapsulate practically poor-soluble drugs within their hydrophobic core. HPLC measurement has demonstrated that HPMA-co-(APMA-Oxadiazole 1%) (O-1) and HPMA-co-(APMA-Dansyl 2%) (D-2) have a higher drug solubilisation capacity than other copolymer formulations.

In vitro release profiles of different model drugs of the optimal formulation of copolymers were investigated at four different temperatures. Unfortunately, these copolymers showed uncontrolled release of all of the loaded drugs. To set-up thermo-responsive copolymers for controlled drug release, approaches based on introducing poly ethylene glycol (PEG) block as a part of O-1 and D-2 amphiphilic copolymers. A significant enhancement in response to the change in temperature as the drug release across the membrane was seen when PEG was present for the three hydrophobic drugs models. Then hybrid nanoparticles (HNPs) were prepared and attached to O-1 as localised nano-heaters to accelerate drug release in responded to temperature change.

Finally, the optimal formulation of (O-1)-b-(PEG) and (O-1)-b-(PEG)-HNPs loaded with paclitaxel (PTX) were tested for their cytotoxicity in vitro on BxPC-3 cells. In-vitro MTT assay results established the ability of (O-1)-b-(PEG)-PTX and (O-1)-b-(PEG)-HNPs-PTX novel formulations to accumulate and kill pancreatic cancer cells more effectively, compared to the free PTX.

Citation

Alsuraifi, A. T. Y. (2018). Hydroxypropylmethacrylamide based thermoresponsive magnetomicelles for controllable drug delivery in pancreatic cancer. (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/412030

• Thesis Type: Thesis
• Publicly Available Date: May 26, 2023
• Keywords: Thermo-responsive drug delivery, Iron oxide-gold nanoparticles, smart polymers
• Public URL: https://keele-repository.worktribe.com/output/412030
• Additional Information: Embargo on access until 1 October 2019 - The thesis is due for publication, or the author is actively seeking to publish this material.
• Award Date: 2018-12