| dc.description.abstract | This study was aimed to investigate the potential applications of hydrophobic-hydrophilic polymers blend as the combination between zein and HPMC 4000 in drug delivery systems including both oral administration and topical administration of poorly-water soluble drugs.
In case of oral administration, isradipine (IDP) and paclitaxel (PTX) were chosen as model drugs owing to their limited aqueous solubility. SDs with different blends of hydrophilic-hydrophobic polymer (zein/HPMC) were prepared to modulate the drug crystal and polymer-drug interaction in SDs. Physicochemical characterizations including powder X-ray diffractometry and Fourier transform infrared spectroscopy (FTIR) were executed to elucidate the roles of blends in SDs. Although hydrophobic polymer played a key role in changing model drug from crystal to amorphous state, the dissolution rate was limited by wetting property. Fortunately, hydrophilic-hydrophobic blend changed drug to be more amorphous for the dissolution rate improvement. Furthermore, as a novel nonionic surfactant and P-glycoprotein inhibitor, the helpfulness of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) in SD demonstrated its ability to optimize the effects of zein/HPMC blends in SD followed by elevating aqueous solubility and hastening dissolution rate, which further enhanced oral bioavailability of administered drugs.
On the other hand, the finding of this research indicated that zein/HPMC blend could be considered as a potential candidate for topical drug delivery. Specifically, this study was also aimed to investigate a new generation of film forming hydrogels loading curcumin-loaded gelatin nanoparticles (CUR-GNPs) for topical application. Film-forming hydrogels (FFHs) were prepared by employing zein and HPMC 4000 as film-forming polymer and gelatinized agent. Meanwhile, CUR-loaded GNPs were obtained by sonoprecipitation method. The film-forming time, particle characteristics, drug release from FFNs and morphology of drying films were assessed. As a result, the optimized FFH provided the drying film achieving smooth surfaces with fast film-forming time of 6 min and 4.5 min in vitro and ex vivo, respectively. Furthermore, the optimal model of CUR-loaded GNPs was examined with a mean diameter of 233.4 nm and the efficiency entrapment was about 50 %. Interestingly, the presence of CUR-loaded GNPs showed the uniform dispersion of CUR-GNPs in FFH throughout morphology study of drying films and high rate of drug permeation after 24 h. Therefore, the FFH containing CUR-loaded GNPs showed potential application for topical drug delivery with fast film-forming time, uniformity of dispersion and high drug sustained permeation.
In conclusion, the finding of this project showed that the potential combination of hydrophilic-hydrophobic blend (zein/HPMC) in designing new generations of drug delivery system.
Keywords: hydrophilic-hydrophobic blend, solid dispersion, film-forming hydrogels, gelatin nanoparticles, poorly-water soluble drugs | en_US |
