Engineering of Nanospheres Dispersed Microneedle System for Antihypertensive Action.

Abstract

A combinational therapy is mostly preferred in hypertension treatment because of low-dose and less side effects like pretibial edema, and gastrointestinal bleeding. So the objective of the present work was to formulate an advanced drug delivery system in the form of bio-responsive microneedles by incorporating nifedipine, a cardiodepressant and diltiazem, a vasodilator for effective synergism in the treatment of hypertension. The pH-responsive PLGA nanospheres of diltiazem were formulated using Water-in-Oil-in- Water (W/O/W) double emulsion and solvent-diffusion-evaporation technique. These nanospheres were added to nifedipine-PVP mixture and then incorporated into mold to develop microneedles. The microneedles showed the release of nifedipine almost 96.93± 2.31% for 24 h due to high PVP solubilization. The nanospheres of diltiazem on contact with acidic pH of skin managed to form of CO2 bubbles and increase the internal pressure to burst PLGA shell due to pore formation. The mean blood pressure observed for the normal group was 89.58 ± 3.603 mmHg, whereas the treatment with the new formulation significantly reduced the mean blood pressure up to 84.11 ± 2.98 mmHg in comparison to the disease control group (109.9 ± 1.825 mm Hg). This system co-delivers the drugs nifedipine and diltiazem in hypertension and shows an advance alternative approach over conventional drug delivery system.