Objective
To develop novel formulation for cardiovascular stent with dual drug using biodegradable polymer. Dual drug combination of Paclitaxel and Aspirin will produce anti-proliferative and antiplatelet effects respectively in atherosclerotic artery of human heart by ascertaining controlled release for prolonged action and efficacy.
Experimental/ Computational work done
The Drug Eluting Stent is a novel drug delivery system which delivers the active ingredient or drug to the site of action after implanted to that specific site which is blocked artery due to atherosclerosis leads to angina. The dual drug-eluting stent (DDES) has been developed by incorporating an anti-proliferative and an anti-thrombotic in a biodegradable polymer-coated onto a stainless steel (316 L) stent using spray coating technique. The DDES is prepared by spray coating the bare metal stent with a biodegradable polymer loaded with Paclitaxel and Aspirin, to treat against restenosis and thrombosis, respectively. Biodegradable polymer such as Poly L Lactide and 95/5 Poly DL Lactide co caprolactone were individually formulated with both drugs to get the desired controlled drug release of both drugs. The sterilized DDES were evaluated for various aspects of morphology by gravimetric method, microscopic and SEM evaluation. The drug content and invitro drug release were evaluated by means of HPLC to established required profile to treat against CAD conditions.
Results and discussion
The DDES was formulated using two different combinations with both drugs one using Poly L Lactide and other using 95/5 Poly DL Lactide co caprolactone. The drug polymer interaction was determined by FT-IR and HPLC. HPLC method was developed to perform simultaneously estimation of Aspirin and Paclitaxel. From the morphological evaluation of stent was done using optical microscopy and SEM, it can be conformed that coating texture and surface was very smooth without any cracks, pits or any other irregularities. The drug loading for 11mm and 39mm stents ere also found to be consistent which proved the precision and repeatability of process and analytical method of estimation. The invitro drug release from 11mm and 39mm using Poly L Lactide were also found to be equivalent and desirable to ascertain good quality and safety.
Conclusions
Incorporation of therapeutic agents like platelet aggregation inhibitors like Aspirin and VSMC (Vascular Smooth Muscle Cell) proliferation inhibitors like Paclitaxel into DES may help in reducing the In-Stent Restenosis (ISR) and improving the safety and efficacy of currently available DES. The delivery of multiple drugs would help in the design of promising therapeutic strategies for the treatment of CAD (Coronary Artery disease) using stent based therapies.
Key words: Dual Drug Eluting Stent, Paclitaxel, Aspirin
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