Modulating chitosan-PLGA nanoparticle properties to design a co-delivery platform for glioblastoma therapy intended for nose-to-brain route

Autor: Leonardo M.B. Ferreira, Fabíola Garavello Prezotti, Sara Granja, Rui Manuel Reis, Maria Palmira Daflon Gremião, Fernanda Isadora Boni, Natália Noronha Ferreira, Beatriz Stringhetti Ferreira Cury, Fátima Baltazar
Přispěvatelé: Universidade Estadual Paulista (Unesp), University of Minho, ICVS/3B’s-PT Government Associate Laboratory, Barretos Cancer Hospital
Rok vydání: 2020
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 2190-3948
Popis: Made available in DSpace on 2020-12-12T01:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Nose-to-brain delivery is a promising approach to target drugs into the brain, avoiding the blood-brain barrier and other drawbacks related to systemic absorption, and enabling an effective and safer treatment of diseases such as glioblastoma (GBM). Innovative materials and technologies that improve residence time in the nasal cavity and modulate biological interactions represent a great advance in this field. Mucoadhesive nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) and oligomeric chitosan (OCS) were designed as a rational strategy and potential platform to co-deliver alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) into the brain, by nasal administration. The influence of formulation and process variables (O/Aq volume ratio, Pluronic concentration, PLGA concentration, and sonication time) on the properties of CHC-loaded NPs (size, zeta potential, PDI and entrapment efficiency) was investigated by a two-level full factorial design (24). Round, stable nano-sized particles (213–875 nm) with high positive surface charge (+ 33.2 to + 58.9 mV) and entrapment efficiency (75.69 to 93.23%) were produced by the emulsification/evaporation technique. Optimal process conditions were rationally selected based on a set of critical NP attributes (258 nm, + 37 mV, and 88% EE) for further conjugation with CTX. The high cytotoxicity of CHC-loaded NPs and conjugated NPs was evidenced for different glioma cell lines (U251 and SW1088). A chicken chorioallantoic membrane assay highlighted the expressive antiangiogenic activity of CHC-loaded NPs, which was enhanced for conjugated NPs. The findings of this work demonstrated the potential of this nanostructured polymeric platform to become a novel therapeutic alternative for GBM treatment. [Figure not available: see fulltext.]. School of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01 Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho ICVS/3B’s-PT Government Associate Laboratory Molecular Oncology Research Center Barretos Cancer Hospital School of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01
Databáze: OpenAIRE
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