Smart Microneedles with Porous Polymer Coatings for pH-Responsive Drug Delivery

Abstract

This work demonstrates a simple approach for coating a porous polymer layer on stainless-steel (SS) microneedles characterized by a pH-responsive formulation for self-regulated drug delivery. For many drug-delivery applications, the release of therapeutic agents in an acidic microenvironment is desirable. Acid-sensitive polymers and hydrogels were extensively explored, but easily prepared polymeric microcarriers that combine acid sensitivity and biodegradability are rare. Here, we describe a simple and robust method of coating a porous polymer layer on SS microneedles (MNs) that release a model drug (lidocaine) in a pH-responsive fashion. It was constructed by packing the model drug and a pH-sensitive component (sodium bicarbonate) into the pores of the polymer layer. When this acid-sensitive formulation was exposed to the acidic microenvironment, the consequent reaction of protons (H+) with sodium bicarbonate (NaHCO3) yielded CO2. This effect generated pressure inside the pores of the coating and ruptured the thin polymer membrane, thereby releasing the encapsulated drug. Scanning electron micrographs showed that the pH-sensitive porous polymer-coated MNs exposed to phosphate-buffered saline (PBS) at pH 7.4 were characterized by closed pores. However, MNs exposed to PBS at pH 5.5 consisted of open pores and the thin membrane burst. The in vitro studies demonstrated the pH sensitivity of the drug release from porous polymer-coated MNs. Negligible release was observed for MNs in receiving media at pH 7.4. In contrast, significant release occurred when the MNs were exposed to acidic conditions (pH 5.5). Additionally, comparable results were obtained for drug release in vitro in porcine skin and in PBS. This revealed that our developed pH-responsive porous polymer-coated MNs could potentially be used for the controlled release of drug formulations in an acidic environment. Moreover, the stimuli-responsive drug carriers will enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity.

Smart Microneedles with Porous Polymer Layer for Glucose-Responsive Insulin Delivery

“…The pore sizes and porosity of the porous coating were adaptable, and a desired porosity could be achieved by adjusting the aqueous sodium bicarbonate to polymer ratio in the coating solution, which in turn controlled the insulin content of the MNs. Increasing the aqueous NaHCO 3 ratio to polymer solution in the emulsion and decreasing the homogenization rate increase the pore size and vice versa reported in our previous study [ 31 , 32 ]. Additionally, the porous coating thickness depends on the polymer concentration in the coating solution and the number of coated layers.…”

Current trends in polymer microneedle for transdermal drug delivery

“…Furthermore, the recent developments focused on the fabrication of smart MNs (bioresponsive) to control drug delivery. In contrast to dissolving and biodegradable MNs, the bioresponsive MNs release the drug smartly according to the change of the physiological signals that achieved by loading of drugs in bioresponsive polymers or encapsulation of drugs in physiological signal sensitive micro- or nanoparticles such as ( Du & Sun, 2020 ) pH-responsive drug release ( Ullah et al, 2019 ), surface activation of nanoparticle that commonly used in cancer treatment ( Chen et al, 2020 , Singh et al, 2019 ), glucose that incorporated with insulin in the tips of MNs array ( Yu et al, 2015 ), reactive oxygen species (ROS)-responsive microneedle (MN) patch for anti-acne therapy ( Zhang et al, 2018a , Zhang et al, 2018b ), and enzymes that triggered or suppress drug release through the inactivity or overexpression of enzymes ( Stern, 2005 , Yu et al, 2018 ).…”

Concept Design of Transdermal Microneedles for Diagnosis and Drug Delivery: A Review

“…Reproduced with permission. [ 168,169 ] Copyright 2012 and 2019, Elsevier BV and MPDI. G–H) Glucose‐responsive MNs.…”