Decitabine enclosed biotin-zein conjugated nanoparticles: synthesis, characterization, in vitro and in vivo evaluation.

Autor: Mhaske, Akshada, Kaur, Jasleen, Naqvi, Saba, Shukla, Rahul
Zdroj: Nanomedicine; 2024, Vol. 19 Issue 21/22, p1743-1760, 18p
Abstrakt: Aim: This study focuses on biotinylated nanocarriers designed to encapsulate amphiphilic molecules with self-biodegradable properties for enhanced drug delivery. Methods: Biotin-zein conjugated nanoparticles were synthesized and tested in C6 cell lines to evaluate their viability and cellular uptake. Optimization was achieved using a a central composite design. The nanoparticles underwent thermogravimetric analysis, and their pharmacokinetics and biodistribution were also studied. Results: The optimized nanoparticles displayed 96.31% drug encapsulation efficiency, a particle size of 95.29 nm and a zeta potential of -17.7 mV. These nanoparticles showed increased cytotoxicity and improved cellular uptake compared with free drugs. Thermogravimetric analysis revealed that the drug-loaded nanocarriers provided better protection against drug degradation. Pharmacokinetic and biodistribution studies indicated that the formulation had an extended brain residence time, highlighting its effectiveness. Conclusion: The biotin-zein conjugated nanoparticles developed in this study offer a promising nano-vehicle for in vivo biodistribution and pharmacokinetic applications. Their high drug encapsulation efficiency, stability and extended brain residence time suggest they are effective for targeted drug delivery and therapeutic uses. Graphical Abstract Article highlights A stable biotin and zein conjugate were formed via ethyl carbodiimide and N-hydroxy succinimide coupling to enhance site-directed delivery. Prepared polymeric conjugates were evaluated for its extent of conjugation, and secondary structural alteration revealed stability of conjugate. The biotin-zein conjugate exhibited a flexible backbone, and better encapsulation of hydrophilic molecules with a sustained release profile. Biotin-zein conjugation improved the loading capacity, and amphiphilic nature and aided the cytotoxic potential of the drug. The conjugated nanocarriers revealed the sustained release profile with higher cytotoxic potential compared with free drug along with enhanced cellular entrapment. The prepared nanoformulation revealed its safety via the nasal mucociliary canal. The formulation suggests higher residence time is observed via the intranasal route of administration compared with intraperitoneal administration. Ex vivo studies revealed presence of fluorescence intensity in the brain at 24 h (intranasal route), whereas in the intraperitoneal administered group signal intensity was reduced. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index