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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Self-assembly of biodegradable copolyester and reactive HPMA-based polymers into nanoparticles as an alternative stealth drug delivery system

Texto completo
Autor(es):
Jaeger, Eliezer [1] ; Jaeger, Alessandro [1] ; Etrych, Tomas [1] ; Giacomelli, Fernando Carlos [2] ; Chytil, Petr [1] ; Jigounov, Alexander [1] ; Putaux, Jean-Luc [3] ; Rihova, Blanka [4] ; Ulbrich, Karel [1] ; Stepanek, Petr [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Acad Sci Czech Republic, Inst Macromol Chem Vvi, Prague 16206 6 - Czech Republic
[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre - Brazil
[3] CNRS, CERMAV, Ctr Rech Macromol Vegetales, F-38041 Grenoble 9 - France
[4] Acad Sci Czech Republic, Inst Microbiol Vvi, Prague 14220 4 - Czech Republic
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: SOFT MATTER; v. 8, n. 37, p. 9563-9575, 2012.
Citações Web of Science: 31
Resumo

The surface modification of nanoparticles by physically anchoring hydrophilic biocompatible polymers is a simple and commercially attractive strategy to produce stealth drug delivery nanocarriers. Herein, we report the preparation, characterization and preliminary evaluation of the biological behaviour of polymeric nanoparticles (NPs) comprising a biodegradable poly(butylene succinate-co-butylene dilinoleate) - PBS/PBDL - copolyester and a non-immunogenic and non-toxic hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. Narrowly distributed sub-100 nm polymeric nanoparticles with stealth properties were successfully prepared by using a combination of interfacial nanoprecipitation and self-assembly. The assemblies were characterized by using complementary scattering techniques and cryo-transmission electron microscopy. The dimension of the NPs was found to be in the proper range to avoid fast renal clearance (D-H > 10 nm) and still below the cut-off size of the leaky pathological microvasculature of hypervascular tumours (D-H < 200 nm), thus making them candidates for application in cancer therapy based on the EPR effect. The presence of PHPMA copolymer exposed at the surface of the nanoparticles was confirmed by scattering measurements. The stealth property of the biocompatible and biodegradable NPs is responsible for their remarkable in vitro stability monitored in a simulated physiological environment and increased stability in concentrated NaCl solutions compared to uncoated PBS/PBDL nanoparticles, making them an alternative to PEG-shielded particles. Furthermore, a reproducible, efficient and satisfactory physical entrapment of the antitumoral drug doxorubicin (DOX) was achieved (similar to 5.0% w(drug)/w(NPs)). The controlled DOX release is pH-dependent and faster under slightly acidic conditions and the cell viability experiments demonstrated that the drug-free NPs are non-toxic, whereas the DOX-loaded NPs exert in vitro cytostatic efficacy on EL4 T cell lymphoma. (AU)

Processo FAPESP: 10/06348-0 - Desenvolvimento de sistemas poliméricos supramoleculares versáteis para aplicação na liberação controlada de agentes antitumorais
Beneficiário:Fernando Carlos Giacomelli
Modalidade de apoio: Auxílio à Pesquisa - Regular