ABSTRACT
BACKGROUND: A combinational therapy is mostly preferred in hypertension treatment because of low-dose and less side effects like pretibial edema, and gastrointestinal bleeding. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: This system co-delivers the drugs nifedipine and diltiazem in hypertension and shows an advance alternative approach over conventional drug delivery system.
Subject(s)
Antihypertensive Agents/administration & dosage , Chemical Engineering/methods , Drug Delivery Systems/methods , Hypertension/drug therapy , Nanospheres/chemistry , Administration, Cutaneous , Animals , Antihypertensive Agents/pharmacokinetics , Blood Pressure/drug effects , Cadmium Chloride/administration & dosage , Cadmium Chloride/toxicity , Chemistry, Pharmaceutical/methods , Diltiazem/administration & dosage , Diltiazem/pharmacokinetics , Disease Models, Animal , Drug Combinations , Drug Delivery Systems/instrumentation , Drug Liberation , Humans , Hydrogen-Ion Concentration , Hypertension/chemically induced , Hypertension/diagnosis , Male , Needles , Nifedipine/administration & dosage , Nifedipine/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Rats , Rats, Wistar , Skin/chemistryABSTRACT
The transdermal route of drug delivery is convenient, pain-free and follows controlled rate release pattern. However, many therapeutically active drugs cannot cross the stratum corneum effectively. Lipophilic drugs like nifedipine cross the outer skin barrier easily and polar drugs, such as epinephrine are ineffective in showing the same effect. Due to these reasons, advancements in drug delivery have taken place to deliver a wide range of drugs, especially macromolecules through the transdermal route and directly into systemic circulation bypassing hepatic metabolism and GIT degradation. So there is a need for advanced drug delivery systems like microneedles and nanoneedles through transdermal route. These tiny needles will also serve as non-toxic, safe and stable systems for advanced drug delivery. Thus, macro to nanoformulation is the fast emerging fields nowadays. These have additional advantages to transdermal patches, such as better penetration, permeation, controlled release and direct delivery to the cytoplasm.
