The physicochemical characteristics of the building blocks influence the physical and biological properties of the PMs [55]. Hence, micelle-forming block copolymers have been the focus of several studies over the past few years. For oral drug delivery system, the block copolymers used to form micelles should (1) spontaneously self-assemble in water, (2) enhance drug solubility by several orders of magnitude and provide high loading efficiency, (3) remain stable upon dilution in the GI tract, (4) be biocompatible and nontoxic, and (5) be easy to synthesize at large scale [28, 56, 57]. The Rapamycin manufacturer choice of core-forming polymers is the major determinant Inhibitors,research,lifescience,medical for important properties of PMs

such as stability, drug loading capacity, and drug release profiles [58]. Poly(propylene oxide) (PPO) [53, 59] which belongs to Pluronics, poly(esters) such as poly(lactic acid) (PLA) [60], hydrophobic poly(amino acids) [61], copolymers of lactic acid and glycolic acids [62, 63], and poly(caprolactone) Inhibitors,research,lifescience,medical (PCL) [64], which are regarded as the commonly used core-forming blocks of PMs, and have been studied in the past 10 years. These core-forming polymers

cover a wide range of structural diversity and polarity for solubilizing numbers of poorly water-soluble drugs Inhibitors,research,lifescience,medical [51, 52]. Meanwhile, the chemical nature and molecular weight of the hydrophilic block will strongly affect the stealth properties and accordingly influence the circulation kinetics Inhibitors,research,lifescience,medical of the micellar assembly. Poly(ethylene glycol) (PEG) is most commonly used as the hydrophilic segment of the block copolymers, since it is a nontoxic polymer with FDA approval

as a component of various pharmaceutical formulations. Furthermore, its unique physicochemical properties (high water solubility, high flexibility, and large exclusion volume) provide good “stealth” properties for PMs [65, 66], while poly(N-vinyl-2-pyrrolidone) (PVP) [67] and poly(acrylic acid) (PAA) [68] are frequently used as PEG alternatives. 4. PMs for Enhancement of Inhibitors,research,lifescience,medical Bioavailability The main mechanisms involved in the enhancement of drug absorption by PMs are: (1) protection of the loaded drug from the harsh environment of the GI tract, (2) Dipeptidyl peptidase release of the loaded drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve drug accumulation [69]. Several physicochemical parameters seem to influence translocation of micelles across the epithelium, including surface hydrophobicity, polymer nature, and particle size [69]. There exist many characteristics of PMs that allow them to traverse across the epithelium. For example, PMs with appropriate particle size can be taken up and then cross the intestinal barrier [40, 70, 71].