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Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer
Akhlesh Kumar Jain1, Hitesh Sahu1, Keerti Mishra1
1School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), India.
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.
Insights
D-Mannose conjugated nanoparticles loaded with 5-Fluorouracil (5-FU) show targeted delivery for liver cancer treatment. These novel nanoparticles enhance drug concentration in the liver, improving efficacy and reducing side effects.
Area of Science:
- Nanotechnology
- Drug Delivery Systems
- Oncology
Background:
- Liver cancer is a significant global health concern with limited effective treatments.
- Conventional therapies for liver cancer cause severe side effects.
- Novel targeted drug delivery systems are crucial for improved localization and reduced systemic toxicity.
Purpose of the Study:
- To design and develop D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs).
- To optimize and characterize these nanoparticles for effective liver cancer treatment.
- To achieve site-specific delivery of 5-FU to liver cancer cells.
Main Methods:
- Preparation and optimization of 5-FU loaded JFSSNPs.
- Conjugation of optimized nanoparticles with D-Mannose.
- Characterization using particle size, morphology, zeta potential, XRD, and DSC.
- Evaluation of in vitro cytotoxicity, in vivo kinetics, and bio-distribution.
Main Results:
- Optimized nanoparticles exhibited particle sizes between 336-802 nm with high drug entrapment efficiency (64.2-82.3%).
- XRD analysis confirmed amorphous incorporation of 5-FU, and DSC indicated no physical interaction with the polymer.
- In vitro studies showed sustained 5-FU release up to 2 hours.
- In vivo studies demonstrated prolonged plasma levels and selective accumulation of 5-FU in the liver.
Conclusions:
- D-Mannose conjugated JFSSNPs are effective carriers for targeted 5-FU delivery in liver cancer.
- These nanoparticles show potential for enhanced therapeutic outcomes and reduced side effects.
- The developed system offers a viable and targeted approach for liver cancer treatment.
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