Pressure Sensitive Adhesives And Polymer Nanoparticles For Transdermal Drug Delivery

Transdermal drug delivery system (TDDS) is a promising therapy instrument and pressure sensitive adhesives (PSA), which act as reservoir and adhesives in this system, may observably influence the curative effect of formulation. In this study, three kinds of hydrophilic pressure sensitive adhesives and two kinds of nanocarrier materials were prepared for technology requirement of TDDS and their properties were investigated.The two-step method was adopted to prepare non-ionic polyurethane pressure sensitive adhesive (PU PSA). It was synthesized by the condensation copolymerization of polymer glycol, diisocyanate and extender. Polyethylene glycol (PEG), which was introduced on the polyurethane chain, can offer good hydrophilicity to the PSA. By physical mixing methods, two types of hybrid hydrophilic PSA, respectively polyvinyl pyrrolidone/polyvinyl alcohol (PVP/PVA) blend system, PVP/ poly (D,L-lactic acid) (PVP/PDLLA) blend system, were prepared. Mechanical testing results show these kinds of adhesives can provide excellent adhesive strength to skin, good humidity permeation behavior and proper water resistance, which are suit for application in TDDS.TGA, DSC and DMA were utilized to analyze the states of water in hybrid hydrophilic PSA , and results reveal that a suitable amount of water (20~35wt%) in hybrid PSA system can enhance strength of hydrogen bonding net work and ensure its flowing deformability for its application as pressure sensitive adhesives. Interaction between components and structure character of hybrid PSA were investigated by choosing PVP/PDLLA system as a sample. UV spectrum, FT-IR spectrum, tensile testing and DSC analysis results indicate that strong hydrogen bonding interaction exists between PVP and PDLLA, and these two polymers can form good miscible blends.The transdermal permeation behaviour of drug from all kinds of PSA matrix was evaluated by using hydrophobic ibuprofen and hydrophilic salicylic acid as model drug. In vitro and in vivo experiment results show that hybrid hydrophilic PSAs facilitate the drug permeating across the rat skin due to their self-enhancing penetration ability, which is more efficient than tradition rubber PSA considering drug permeation amount. Paclitaxel-loaded methoxy poly(ethylene glycol)-b-poly(D,L-lactic acid) diblock copolymer nanoparticles (PMT) were prepared by solid dispersion technique and D,L-tetrahydropalmatine (THP)-loaded poly{[α-maleic anhydride-ω-methoxy- poly(ethylene glycol)]-co-(ethy cyanoacrylate)} (PEGECA) amphiphilic graft copolymer nanoparticles (PEGECAT NPs) were prepared by the nanoprecipitation technique. The transdermal permeation experiments in vitro were carried out in Franz diffusion cells using drug-loaded nanoparticles as donor system. HPLC, TEM, FT-IR and 1HNMR were used to assay the receptor fluid. The results showed that these two kinds of amphiphilic copolymer nanoparticles with the entrapped drug were able to penetrate the rat skin. Fluorescent microscopy measurements indicate that the nanoparticles can penetrate the skin not only via appendage routes but also via epidermal routes. This nanotechnology may provide transdermal feasibility for the drug which is hard to permeate across skin.