Design And Synthetic Of Ph Sensitive Nano Micelles For Poorly Water Soluble Oral Drugs

For oral drug delivery, pH-sensitive micelles can enhance drug solubility by several orders of magnitude and provide high loading efficiency, remain stable upon dilution in the GI tract, be biocompatible and non toxic, easy to synthesize at large scale, also can realize pH controlled release of drugs, minimize the initial burst release in the acidic stomach and release the drug with a molecularly dispersed form in the small intestine, and has been one of the most prospective poorly water soluble drug delivery systems.pH-sensitive polymeric micelles poly(polylactide-co-methacrylic acid)-b-poly (acrylic acid) was synthesized in this paper, by the atom transfer radical polymerization and ring opening polymerization. By changing the monomer feed ratio, adjusting the structure of polymer, four polymers were prepared with different ratio of hydrophilic block and hydrophobic block:P (PLAMA10-co-MAA45)-b-PAA10, P (PLAMA10-co-MAA58)-b-PAA20, P (PLAMA10-co-MAA58)-b-PAA10, P (PLAMA20-co-MAA58)-b-PAA10.The molecular structures and characteristics of the polymers were confirmed by GPC,1H NMR, and FT-IR. Studied the properties of the polymeric micelle and pH response behavior.The CMC of the polymeric micelles were confirmed by fluorescence probe method, the CMC was decreased with the increase of hydrophobic block length. As the decrease of the pH value, the particle size increase with the decrease of the first, zeta potential by negative value tending to zero, a pH-dependent phase transition behavior produces: swelling-shrinkage--gathering.Study the influence of polymeric micelle structure on the drug loading capability, to exploring the mechanism of the drug loading. In a certain range, with the increase of hydrophobic block ratio, polymer micelle absolute value of zeta potential decrease, the CMC values increase, The repulsive interaction between micelle and drug is weakened, the drug-packaged capability of micelle core increases, the drug loading capacity and encapsulation efficiency of micelle increase from 4.6%,20.5% to 6.7%,26.2% respectively.Explore the pH controlled release behaviour of polymeric micelles. Under the environment of SIF (pH 7.36), the cumulative released of NFD can reach 80% in 24h, while only 35% in the SGF (pH 1.35). It is suggested that polymeric micelles P (PLAMA-co-MAA)-b-PAA has an excellent capability of pH-response controlled release, which can protect drugs from the SGF’s destruction and release the drug in the small intestine. As a result, P (PLAMA-co-MAA)-b-PAA makes a big difference to improving the oral bioavailability of drugs.