A Novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery

Presented By:

Mr. Nitin P. Kanwale M. Pharm. (Quality Assurance)

MVP-SAMAJ’S COLLEGE OF PHARMACY, NASHIK02.

Content

Introduction

Synthesis of Modified protein

Preparation of Modified Lipid Nanocarrier

Characterisation

Cytotoxicity Study

Conclusion

References

Introduction

Lipoprotein Based Nanocarrier in tumor cell targeting

NEED OF LIPOPROTEIN

MIMIC NANOCARRIER

Objective of Research

Develop the Nanocomplex that mimic the structure of lipoprotein

To achieve Tumour cell targeting

To overcome shortages of lipoprotein

Modified protein-lipid nanocomplex

The mP-LNC was composed of a shell of selectable targeting ligand modified protein with amphiphilic phospholipid and a core of hydrophobic lipids.

Synthesis and characterization of ursodeoxycholic acid modified BSA

The carboxyl group of ursodeoxycholic acid (UA) was reactivated by EDC and NHS and then covalently attached to the lysine residues of BSA.

• Degree of substitution of modified BSA • Molecular weight of modified BSA

• Surface tension measurement of modified BSA

Preparation of modified protein–lipid nanocomplex (mP-LNC)

LNP was composed of PC (phosphatidylcholine), MCT (medium chain triglycerides), octadecylamine (OL) and hydrophobic drug. nP-LNC was prepared by incubating natural BSA with LNP. mP-LNC included uP-LNC and cP-LNC, respectively prepared by incubating UA modified BSA (uP) and CH modified BSA (cP) with LNP.

Characterization of mP-LNC and LNP

Morphology, particle size and zeta potential

Determination of loading efficiency

WcWN *

100DLE%=

In vitro release of coumarin-6 from nanoparticles

Cytotoxicity and cell uptake test in vitro

Panels a–c were the fluorescence microscopy images of L02 cells after incubation with (A) LNP, (B) c60P-LNC and (C) u60P-LNC (with 100 μg/mL of nanoparticle concentration)at 37 °C for 2 h. Panels d–f were the fluorescence microscopy images of Bel 7402 cells after incubation with (D) LNP, (E) c60P-LNC and (F) u60P-LNC (with 100 μg/mL of nanoparticleconcentration) at 37 °C for 2 h. Panels g–i were the fluorescence microscopy images of HepG2 cells after incubated with (G) LNP, (H) c60P-LNC and (I) u60P-LNC (with 100 μg/mL ofnanoparticle concentration) at 37 °C for 2 h.

Conclusion

A novel modified protein–lipid Nano complex was developed inthis study.The targeting effect of the protein–lipid Nano complex was preliminarily proved by using coumarin-6 as fluorescence probe in normal and cancer liver cells. It was observed that the uptake of uP-LNC in hepatoma cells significantly increased compared with that of cP-LNC or LNP, and was much more in cancer cells than in normal cells. It indicated that the recognition of UA and bile acid receptor played an important role in the targeting delivery.

Review

References

Ying Xu, Xuefeng Jin, Qineng Ping , Juan Cheng, Minjie Sun, A ⁎novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery, Journal of Controlled Release 146 (2010) 299–308