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Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

[ Vol. 18 , Issue. 3 ]

Author(s):

Akhlesh Kumar Jain*, Hitesh Sahu, Keerti Mishra and Suresh Thareja   Pages 369 - 380 ( 12 )

Abstract:


Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery.

Background: Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues.

Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer.

Materials and Methods: 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies.

Result and Discussion: 5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug.

Conclusion: In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Keywords:

5-Fluorouracil, liver cancer, nanoparticles, Jackfruit seed starch, D-Mannose conjugated nanoparticles, Hep G2 cell lines.

Affiliation:

School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda-151 001 Punjab

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