In vitro and in vivo evaluation of gliclazide push-pull osmotic pump coated with aqueous colloidal polymer dispersions.

The objective of present work was to design and evaluate gliclazide push-pull osmotic pump (PPOP) coated with aqueous colloidal polymer dispersions-Eudragit(®) RL 30D and Eudragit(®) RS 30D. The influence of diacetin, diethyl phthalate (DEP), dibutyl sebacate (DBS) and triethyl citrate (TEC) on the free Eudragit(®) RL 30D and Eudragit(®) RS 30D films as plasticizers on drug release were studied. Among these four plasticizers, diacetin offered the smoothest surface of the cast films, and it displayed greatest water vapor transmission coefficient. Free RL and RS films with diacetin also exhibited greatest erosion compared with the other three plasticizers. On the other hand, TEC, DEP and DBS showed greater water absorption. When compared with CA-coated gliclazide PPOP, Eudragit-coated ones showed a f(2) factor of 71.7, indicating the similarity between the release profile of the two formulations. The prepared Eudragit-coated gliclazide PPOP showed typical Zero-order release characteristics, with R being 0.9953. In the in vivo evaluation, the mean relative oral bioavailability of Eudragit-coated PPOP compared to CA-coated ones was 106.9%, demonstrating good bioequivalence. Both of their in vitro-in vivo correlation (IVIVC) showed linear relationship, with R(2) being 0.9955 (Eudragit-coated PPOP) and 0.9987 (CA-coated PPOP), respectively. These results suggested that PPOP coated with Eudragit(®) RL 30D and RS 30D could overcome drawbacks of organic solution coating and promote the development of PPOP.

A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro.

The epidermal growth factor receptor (EGFR) serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD) that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC) and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.