A Novel Polymer-Lipid Hybrid Nanoparticle for the Improvement of Topotecan Hydrochloride Physicochemical Properties

Author(s): Emanuelle Jesus Silva, Leonardo Gomes Souza, Luis Antonio Dantas Silva, Stephania Fleury Taveira, Raquel Ciffarello Guilger, Luciano Morais Liao, Luiz Henrique Keng Queiroz Junior, Mabio Joao Santana, Ricardo Neves Marreto*.

Journal Name: Current Drug Delivery

Volume 15 , Issue 7 , 2018

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Graphical Abstract:


Background: Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting alternatives to improve TPT nanoencapsulation.

Objective: This study seeks to prepare complexes between the cationic TPT and the negatively charged dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control.

Methods: The optimum ionic molar ratio in DS-TPT complexation was determined, and the selected complex was characterized by FTIR and solid-state 13C NMR. TPT solubility in the free and complexed forms was also assayed. TPT-PLN was then obtained via a microemulsion technique, and particle size, zeta potential, encapsulation efficiency, drug loading and drug recovery were determined. Additionally, the TPT stability and in vitro release were determined from PLN and compared with free TPT, TPT-DS complex and TPT encapsulated in nanostructured lipid carriers (NLC) of similar composition.

Results: TPT-DS complexation was confirmed by FTIR and NMR. TPT solubility in the complex was drastically decreased when compared to free TPT. TPT-PLN had high encapsulation efficiency (97%) and drug loading capacity (5.5%). Additionally, TPT-PLN showed a mean diameter, polidispersivity index e zeta potential of 140 nm, 0.2 and -22 mV, respectively. The TPT chemical stability and release from PLN were observed to be superior when compared to NLC.

Conclusion: PLN has shown to be a more effective nanosystem for TPT nanoencapsulation because TPT loading, stability and release were superior when compared to TPT-NLC.

Keywords: Topotecan, polymer-lipid hybrid nanoparticle, dextran sulfate, complexation, drug stability, prolonged drug release.

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Article Details

Year: 2018
Page: [979 - 986]
Pages: 8
DOI: 10.2174/1567201815666171215110026
Price: $65

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