Poly (methacrylic acid)‐based molecularly imprinted polymer nanoparticles containing 5‐fluourouracil used in colon cancer therapy potentially

Abstract

The objective of this work was to synthesize molecularly imprinted polymer (MIP) nanoparticles based on methacrylic acid (MAA) monomer with a high selectivity against an anti-cancer drug, 5-fluorouracil (5-FU), as a template. In this case, the nanoparticles were prepared via precipitation polymerization in the presence of ethylene glycol dimethacrylate as cross-linker and azobisisobutyronitrile as initiator. Besides, 3 independent variables including MAA: 5-FU molar ratio (X 1 ), temperature (X 2 ), and time (X 3 ) were investigated utilizing response surface methodology. The scanning electron microscopy and dynamic light scattering resulted the average diameter of approximately 65 nm, and the MIP nanoparticle sample with the imprinting factor of 1.57 was polymerized in optimized conditions as follows: X 1 = 6: 1, X 2 = 60°C, and X 3 = 3 days in acetonitrile as porogenic solvent. Also, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis confirmed the formation of MAA/5-FU complex and lower thermal stability of the washed MIP sample than the unwashed MIP and non-imprinted polymer (NIP) samples, respectively. Moreover, the optimized MIP nanoparticles have more controlled release of 5-FU rather than the NIP sample. Finally, the flow cytometry showed that 5-FU-loaded MIP sample has the highest apoptosis of human colon cancer cell line, HCT-116, after 3 days compared with NIP sample and also the exclusive use of drug.

Molecularly Imprinted Polymer Nanoparticles: An Emerging Versatile Platform for Cancer Therapy

“…One example is a carbazole derivative released from a magnetic nanoMIP prepared with methacrylic acid as the functional monomer and 1,4‐dimethyl‐6‐hydroxy‐9 H ‐carbazole as the template molecule for controlled antitumor drug delivery [48] . Compared to the NIP which displayed total drug release in about 6 h, the nanoMIP prolonged the drug release for more than 48 h. Similar results were also reported by Neda et al., where a 5‐fluourouracil‐templated nanoMIP exhibited a sustained release for more than 96 h, four times longer than the NIP counterpart [49] …”

Molecularly Imprinted Polymer Nanoparticles: An Emerging Versatile Platform for Cancer Therapy

“…[48] Compared to the NIP which displayed total drug release in about 6 h, the nanoMIP prolonged the drug release for more than 48 h. Similar results were also reported by Neda et al, where a 5-fluourouracil-templated nanoMIP exhibited a sustained release for more than 96 h, four times longer than the NIP counterpart. [49] Noncovalent forces (including hydrogen bonding, van der Waals forces, and hydrophobic interactions) are generally responsible for the affinity of MIPs to templates. The sensi- Columns from left to right: SA-, Fuc-, and Man-imprinted nanoparticles.…”

Perspectives of Molecularly Imprinted Polymer-Based Drug Delivery Systems in Cancer Therapy

“…Since its carboxyl group can develop weak electrostatic interactions and/or can act as a hydrogen donor for N, O, or S containing drugs, methacrylic acid (MAA) remains the most frequently used functional monomer in the non-covalent molecular imprinting protocols for DDS development. Several anticancer drugs were successfully imprinted using MAA, i.e., 5-fluorouracil (5-FU) [51][52][53], CAP [54], paclitaxel (PCX) [55][56][57][58][59], thalidomide [60,61], mitoxantrone [62], and sunitinib (SUT) [63]. Moreover, as it can be inferred from Table 2, the bulk of protocols employed ethylene glycol dimethacrylate (EDMA), an acrylic crosslinker Polymers 2019, 11, 2085 7 of 33 characterized by low biocompatibility and no biodegradability, and therefore with limited perspectives in drug delivery development [64].…”