A Novel Microfluidic Assembly of a Biodegradable Nanostructures Designed for Site Specific Delivery of Anticancer Peptide Site Specific Delivery of Anticancer Peptide

Ahmed M Faheem,Mohamed Eltanani,Samuel M Girgis,Amal Ali Elkordy

doi:10.5920/bjpharm.601

Abstract

Ran is a small RAS-related GTPase and is overexpressed in breast carcinoma to induce malignant transformation and metastatic growth. A novel series of antiRan-GTPase peptide (CK-10), which inhibits Ran hydrolysis and activation, have suboptimal activity in vitro due to low bioavailability and poor delivery. To overcome these disadvantages, we delivered the CK-10 peptide by encapsulating it in PLGA-based nanoparticles (NP). The successful delivery of CK-10 can prevent Ran activation by blocking a regulator of chromosome condensation 1 (RCC1) following peptide release directly in the cytoplasm after endocytosis of the novel NP(s). A novel hydrodynamic flow technique is designed to avoid the drawbacks with a double emulsion solvent evaporation technique. Loading efficiency and in vitro release were measured by modified Lowry assay, size was characterized by dynamic light scattering, tuneable pore resistive sensing and laser obscuration time, zeta potential was measured by laser anemometry, morphology was scanned by electron microscopes and laser obscuration time. Water absorption and its associated changes in the physicochemical properties were measured by various color indicator and potentiometric titration techniques tounderstand the fundamental biodegradation process. PLGA/β-cyclodextrin nanoparticles showed the highest peptide loading (53.92%m/m) for the novel microfluidic technique with the highest cumulative release of 91.38%.

Highlights

Nanocarriers can escape the reticuloendothelial system (RES), which attacks any foreign material by opsonisation, tracked by macrophage phagocytosis
All the chemicals were purchased from Sigma Aldrich UK and the novel CK-10 peptide was purchased from a GL Biochem in China
The particle size was measured by dynamic light scattering (DLS), tunable pore resistive sensing technique (TPRS) and laser obscuration time (LOT) techniques while zeta potential was measured by laser

Summary

SUMMARY

Ran is a small RAS-related GTPase and is overexpressed in breast carcinoma to induce malignant transformation and metastatic growth. A novel series of antiRanGTPase peptide (CK-10), which inhibits Ran hydrolysis and activation, have suboptimal activity in vitro due to low bioavailability and poor delivery. To overcome these disadvantages, we delivered the CK-10 peptide by encapsulating it in PLGA-based nanoparticles (NP). The successful delivery of CK-10 can prevent Ran activation by blocking a regulator of chromosome condensation 1 (RCC1) following peptide release directly in the cytoplasm after endocytosis of the novel NP(s). PLGA/β-cyclodextrin nanoparticles showed the highest peptide loading (53.92%m/m) for the novel microfluidic technique with the highest cumulative release of 91.38%

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION