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Multicompartimental Nanoparticles for Co-Encapsulation and Multimodal Drug Delivery to Tumor Cells and Neovasculature

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ABSTRACT

Purpose

The purpose of this work was the development of a multicompartimental nanocarrier for the simultaneous encapsulation of paclitaxel (PTX) and genistein (GEN), associating antiangiogenic and cytotoxic properties in order to potentiate antitumoral activity.

Method

Polymeric nanocapsules containing PTX were obtained by interfacial deposition of preformed polymer and coated with a phospholipid bilayer entrapping GEN. Physical-chemical and morphological characteristics were characterized, including size and size distribution, drug entrapment efficiency and drug release profile. In vivo studies were performed in EAT bearing Swiss mice.

Results

Entrapment efficiency for both drugs in the nanoparticles was approximately 98%. Average particle diameter was 150 nm with a monomodal distribution. In vitro assays showed distinct temporal drug release profiles for each drug. The dose of 0.2 mg/kg/day of PTX resulted in 11% tumor inhibition, however the association of 12 mg/kg/day of GEN promoted 44% tumor inhibition and a 58% decrease in VEGF levels.

Conclusions

Nanoparticles containing GEN and PTX with a temporal pattern of drug release indicated that the combined effect of cytotoxic and antiangiogenic drugs present in the formulation contributed to the overall enhanced antitumor activity of the nanomedicine.

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Abbreviations

BS:

Backscattering

CCT:

Capric/caprylic triglyceride

EAT:

Ehrlich ascites tumor

EE:

Encapsulation efficiency

FDA:

Food and drug administration

GEN:

Genistein

HPLC:

High performance liquid chromatography

i.p.:

Intra peritoneal

NC:

Uncoated nanoparticles

NC-PC:

Coated nanoparticles

NP:

Nanoparticles

NTA:

Nanoparticle tracking analysis

PBS:

Phosphate buffered saline

PdI:

Polydispersity index

PLGA:

Poly(lactic-co-glycolic acid)

PTX:

Paclitaxel

PVDF:

Polyvinylidene difluoride

SLS:

Sodium lauryl sulfate

T:

Transmission

TEM:

Transmission electron microscopy

VEGF:

Vascular endothelial growth factor

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the Brazilian research funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Pesquisas (FINEP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio à Pesquisa da Universidade Federal de Goiás (FUNAPE) and Fundação de Apoio à Pesquisa do Estado de Goiás (FAPEG).

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Authors and Affiliations

  1. Laboratório de Nanotecnologia Farmacêutica e Sistemas de Liberação de Fármacos–FarmaTec, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, GO, Brazil

    Lívia Palmerston Mendes, Marilisa Pedroso Nogueira Gaeti, Lílian Cristina Rosa dos Santos & Eliana Martins Lima

  2. Laboratório de Farmacologia e Toxicologia Celular–FarmaTec–Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, GO, Brazil

    Paulo Henrique Marcelino de Ávila, Marcelo de Sousa Vieira, Bruna dos Santos Rodrigues, Renato Ivan de Ávila Marcelino & Marize Campos Valadares

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  1. Lívia Palmerston Mendes
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  2. Marilisa Pedroso Nogueira Gaeti
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  3. Paulo Henrique Marcelino de Ávila
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Correspondence to Eliana Martins Lima.

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Mendes, L.P., Gaeti, M.P.N., de Ávila, P.H.M. et al. Multicompartimental Nanoparticles for Co-Encapsulation and Multimodal Drug Delivery to Tumor Cells and Neovasculature. Pharm Res 31, 1106–1119 (2014). https://doi.org/10.1007/s11095-013-1234-x

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  • DOI: https://doi.org/10.1007/s11095-013-1234-x

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