Drug release using pH-responsive drug delivery system

Abstract

The colloid phenomenon of soft particles is becoming an important area of research due to the growing interest in using polymeric systems for drug delivery applications. The former studies have focused on techniques that required the intermediate steps of dialysis or centrifugation, whereas, in this study, a drug selective electrode (DSE) was used to directly measure the concentration of procaine (PrHy) or imipramine (IMI) hydrochloride released from pH-responsive colloidal particles, thereby eliminating the intermediate step. The PrHy and IMI selective membrane exhibited excellent reproducibility and stability. With a single drug delivery system (methacrylic acid-ethyl acrylate (MAA-EA) nanogel), release of two different drugs loaded by distinctly different interactions was demonstrated. PrHy was found to be hydrophobically bounded, while IMI was bounded electrostatically to the MAA–EA nanogels, which were further enhanced by hydrogen bonding. The different kinds of interactions produced different release kinetic profiles. Mathematical fitting of the release kinetic profiles to the Berens and Hopfenberg model allowed the quantification of parameters that describe the contributions of chain relaxation and diffusion process. A balance between chain relaxation and Fickian diffusion process controls the release of drugs from these pH-responsive nanogels. The coated nanogels with encapsulated drugs were successfully prepared by layer by layer (LBL) assembly approach. The initial burst release behavior observed in the nanoparticles was minimized and eliminated by the introduction of several polyelectrolyte layers. Through this LBL approach, the permeability of nanogels was altered and with each additional polyelectrolyte layer, the time to achieve the steady state drug concentration increased linearly with the number of polyelectrolyte layer. LBL coating of responsive nanogels provided an elegant solution that may be suitable for designing nanoparticles for drug delivery applications, where the high initial burst release and short therapeutic time range can be adequately managed. pH-responsive nanogels with varying glass transition temperature (Tg) were synthesized via emulsion polymerization for elucidating the effect of swelling on the drug release. With a higher chain rigidity (high Tg), the swelling ability of the nanogels was reduced, which would have a significant effect on the release of PrHy. With a lower swelling capacity (higher Tg), the porosity of the nanogels was minimized resulting in a slower release of the drugs from the nanogels. The DSE was proven to be a versatile and simple technique to quantify the release kinetic profiles of the cross linked nanogel system.