Electrically controlled drug release using pH-sensitive polymer films

Abstract

Drug delivery systems (DDS) that allow spatially and temporally controlled release of drugs are of particular interest in the field of drug delivery. These systems create opportunities for individually tailored doses of drugs to be administered as well as reduce side effects by localizing the initial drug dose to the organ of interest. We present an electroresponsive DDS in the form of a bioresorbable nanocomposite film which operates at low voltages (<-2 V). The method is based on electrochemically generating local pH changes at an electrode surface to induce dissolution of a pH-sensitive polymer, which is used as the carrier material. We previously demonstrated this proof-of-concept using a poly(methyl methacrylate-co-methacrylic acid) (co-PMMA) copolymer commercially marketed as Eudragit S100 (EGT). However, as EGT is soluble at a pH above 7, experiments were performed in isotonic saline solutions (pH ∼ 6.4). In this work, we have synthesized co-PMMA with a variety of monomer ratios to shift the solubility of the copolymer to higher pH values, and developed a polymer that can be used under physiologically relevant conditions. The generalizability of this system was demonstrated by showing controlled release of different drug molecules with varying parameters like size, hydrophobicity, and pKa. Fluorescein, a hydrophilic model compound, meloxicam, a hydrophobic anti-arthritic medication, curcumin, a small molecule with anti-cancer therapeutic potential, and insulin, a polypeptide hormone used in the treatment of hypoglycemia, could all be released on demand with minimal leakage. The drug loading achieved was ∼32 wt% by weight of the co-polymer.

Targeted delivery of poly (methyl methacrylate) particles in colon cancer cells selectively attenuates cancer cell proliferation

“…Polymeric nanocarriers are found to be effective in safe drug delivery because its hydrophobic core which helps in the dissolution of hydrophobic drugs [14]. Among the different types of hydrophobic polymers, PMMA is widely used in drug delivery applications [15][16][17][18]. PMMA is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and most important is that it does not cause toxicity [19].…”

Electrochemically Generated Interfacial pH Change: Application to Signal‐Triggered Molecule Release

“…Another system was based on the dissolution of a polymer matrix loaded with biomolecules or drugs, thus resulting in their release when local pH value was altered upon electrochemical water reduction. [52] A Au electrode surface was coated with poly(methyl methacrylate-co-methacrylic acid) layer loaded with various target molecules. In order to stabilize the polymer-matrix and inhibit uncontrolled leakage of the loaded molecules, the polymer film was additionally coated with a chitosan layer, Figure 6A.…”

“…The data shown in parts (B) and (C) also originates from Ref. [52]. electrode surface was analyzed by confocal fluorescent microscopy and quartz crystal microbalance (QCM) measurements.…”

Nanocontrollers for In Vitro Drug Release Based on Core‐Sheath Encapsulation of Theophylline into Hydroxypropyl Methylcellulose Acetate Succinate Nanofibers

“…Thus, sustained release can be realized at the same time. Other researchers have paid attention to preparing pH stimulus‐responsive drug vehicles with nanostructures such as nanocomposites, 22 nanovalves, 23 nanoparticles, 13,24 nanogels, 1 nanofibers 25 and so on. In these structures, nanofibers have shown more prominent performances because of their greater specific area and very high length‐to‐diameter ratio 26,27 .…”