Microwave-assisted Synthesis of Molecularly Imprinted Polymer for Sustained Drug Release: A Chemometric Approach on Polymer Synthesis and Rebinding Study

Vannessa, Lawai (2024) Microwave-assisted Synthesis of Molecularly Imprinted Polymer for Sustained Drug Release: A Chemometric Approach on Polymer Synthesis and Rebinding Study. PhD thesis, Universiti Malaysia Sarawak.

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Abstract

Molecularly imprinted polymers (MIP) have garnered significant interest as drug delivery system (DDS) in recent years. The conventional thermal heating and one-variable-at-a-time method for synthesising MIP and rebinding capacity evaluation is resource- and time-consuming. Thus, this study focused on the response surface methodology (RSM) optimisation of the polymer synthesis using microwave (MW)-assisted and comparing with conventional thermal synthesis. The influence of two factors (methacrylic acid and divinylbenzene concentration) was studied on the response of the MIP rebinding capacity. Further optimisation on rebinding capacity were employed three factors including MIP dosage, initial drug concentration and contact time using Central Composite Design (CCD). In vitro drug release profiles were evaluated in pH 7.4 and pH 2.2 of dissolution media. The aspirin MIP showed spherical particles with smaller particle sizes (500 nm– 1.45 μm) and yields (0.5–1 g) via MW-assisted synthesis (sample id: ASDW) as compared to the conventional synthesis (sample id: ASD) (size 660 nm –3.65 μm, yield 0.5–1.15 g). The MW-MIP of paracetamol (sample id: PCMW) also showed similar findings with ASDW (size 1.07 – 1.64 μm, yield 0.5 - 0.9 g). The optimised formulation of MIP showed polymer P1 with T:FM:CL of 1:4:16 have shown high rebinding capacity in both polymerisation methods of conventional thermal heating (ASD-P1, 3.00±0.31mg/g)and MW-assisted synthesis (ASDW-P1, 7.05±0.08 mg/g; PCMW, 6.17±0.03 mg/g). The optimal rebinding conditions for ASD-P1, ASDW-P1 and PCMW-P1 to achieve high rebinding capacity are as follows: 240 min contact time, 300 mg/L initial concentration and 20 mg MIP dosage. Method validations were performed under optimised conditions and showed only 2-3% error compared with the predicted rebinding capacity. The drug release profile for ASD-P1, ASDW-P1 and PCMW-P1, has shown a sustained drug release with the highest cumulative release observed at pH 7.4 (64 – 78% for 24 h) than at pH 2.2 (44 – 76%, for 24 h). The release of aspirin and paracetamol at pH 2.2 was fitted in first-order kinetics, followed by the Higuchi model. Meanwhile, all MIP (ASD-P1, ASDW-P1 and PCMW-P1) at pH 7.4 were well-fitted with the Higuchi model. These results collectively demonstrated that the MIP performances are impacted by the choice of the MIP composition (i.e., functional monomer and crosslinker) and the polymerisation method (i.e., MW-assisted synthesis, conventional thermal heating). The optimised formulation ratio of MIP at ratio 1:4:16 can significantly enhance the efficacy, precision, and safety of drug delivery systems, making MIP a valuable component in modern pharmaceuticals. Furthermore, the optimised MIP can potentially reduce cost associated with drug formulation.

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