Gelatin-PVP dissolving microneedle-mediated therapy for controlled delivery of nifedipine for rapid antihypertension treatment.

Nifedipine has exhibited to be the oldest primary drug having promising therapeutic potential for hypertension, angina pectoris, and pre-eclampsia treatment which are the most emergency serious complications worldwide. Moreover, for long-term treatment transdermal route of delivery using polymeric dissolving microneedles (DMNs) patches has shown greater advantages, thus enhancing treatment compliance, painless, reducing the daily number of doses, prolonged release in a controlled manner, and variable bioavailability making this an ideal candidate for the transdermal therapeutic system. Here, we fabricated DMN patches made of gelatin and PVP using PDMS molds loaded with nifedipine drugs for a controlled painless delivery for a longer stable duration. The prepared gelatin-PVP (gel-PVP) DMN patches loaded with nifedipine were fabricated by centrifugation casting method. The characterization results displayed excellent mechanical strength of the needles to penetrate the skin. SEM and confocal microscopy showed penetration of the needles up to 567-600 µm using rhodamine B applied to the hairless punctured skin site. FTIR study exhibited no degradation of the drug was observed while fabricating the DMNs patch at different pH 7.4 and 4. Skin resealing test proved that there was immediate resealing of the skin observed within 10-15 min. Further in-vitro drug release profile study was carried out by dissolution method at different pH 7.4 and 4 showed sustained release of the drug up to 96 ± 2% till 48-72 h avoiding polymer or drug loss which was quantified by UV vis spectrophotometer at 235 nm absorbance showed stable release of the drug upto 48-72 h. A stability study carried out by the HPLC method showed the DMN patches loaded with the drug were found to be stable for up to 30 days at 25 °C. This novel preliminary data are the first study to our knowledge introducing these fabricated nifedipine gel-PVP DMN patches were found to be very efficient and showed prolonged controlled release up to 48-72 h thereby treating hypertension in a convenient, painless manner. This DMN patch-formulated design might act as a potential approach leading to a controllable, self-administrative, and rapid transdermal delivery system.

Synthetic enzyme-based nanoparticles act as smart catalyst for glucose responsive release of insulin.

BACKGROUND: Earlier studies have attempted to create electronic free insulin delivery systems using different glucose sensing mechanism, no successful clinical translation as hitherto been made. This study aimed to assess the faster responsiveness of the insulin release from this enzyme based nanoparticles which is a self-regulated insulin delivery system constructed by loading with insulin, enzyme glucose oxidase into hyaluronic acid and 2-nitroimidazole forming enzyme-based nanoparticles which works in accordance to the blood glucose level. MATERIALS AND METHOD: Enzyme-based nanoparticles were prepared by ionic gelation method. Insulin content in the nanoparticles kept for stability study was estimated by human insulin enzyme based immunosorbent assay. In in-vitro studies; different concentrations of glucose were taken and the release study of insulin was recorded. RESULTS: This enzyme-based nanoparticles were having average diameter of around 193 nm and stability studies showed that nanoparticles were stable upto 30 days at 4 °C. In-vitro studies showed the release of insulin from nanoparticle conjugates which was effectively correlated with the external glucose concentration created where different concentrations of glucose taken thus facilitating the stabilization of blood glucose levels in the hyperglycemia state which was achieved within 10 min. (400 mg/dL) wherein drug release rate remarkably increased in hyperglycemia state and no specific changes or small amount of release was observed in normoglycemia state (100 mg/dL). CONCLUSION: Overall, this preliminary study of this enzyme-based nanoparticles formulation showed excellent rapid responsiveness towards hyperglycemia which might act as a potential biomimetic system in triggering the release of insulin in sustained manner.

Microneedle - Future prospect for efficient drug delivery in diabetes management.

This review aims at focusing on the use of microneedles (MNs) as an emerging novel drug delivery carrier for an effective treatment in diabetic patients. There are many limitations in various modes of delivery such as oral, subcutaneous, nasal, and other modes which cause pain and have many other side effects. Hence, this drug delivery research has found to have tremendous potential in combining both the diagnostic and therapeutic elements, thus treating diabetes in a better way. Most glucose-sensing techniques and conventional insulin therapies are engaged in the transfer of physical entities through the skin. MN- based drug delivery system can accomplish in an noninvasive or minimally invasive manner which can be an add on advantage towards pain-free administration, easy handling, discrete, continuous as well as providing a controlled release system. Hence, the review addresses on the current advancement of this bioengineered system like MNs, constituting a "smart" system specifically for autonomous diabetes therapy.