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Título

Conjugation of cell-penetrating peptides with poly(Lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

AutorVasconcelos, Aimee C.; Vega, Estefanía; Pérez, Yolanda; Gómara, María José; García, Marisa Luisa; Haro, Isabel
Palabras claveAnti-inflammatory
Ocular tolerance
Controlled release
Flurbiprofen
Peptide for ocular delivery
Fecha de publicación27-ene-2015
EditorDove Press
CitaciónInternational Journal of Nanomedicine
ResumenIn this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)- polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavail- ability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG- peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confrmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flur- biprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory effcacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment effciency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective preven- tion of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test-chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery.
Versión del editorhttp://dx.doi.org/10.2147/IJN.S71198
URIhttp://hdl.handle.net/10261/130255
DOI10.2147/IJN.S71198
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