INVESTIGADORES
ROMERO eder Lilia
artículos
Título:
Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels
Autor/es:
ANA PAULA PEREZ, CECICLIA MUNDIÑA-WEILENMANN, EDER LILIA ROMERO, MARIA JOSE MORILLA
Revista:
INTERNATIONAL JOURNAL OF NANOMEDICINE
Editorial:
DOVE MEDICAL PRESS LTD
Referencias:
Lugar: Auckland; Año: 2012 vol. 7 p. 1373 - 1385
ISSN:
1176-9114
Resumen:
Background: Molecules taken up by olfactory and trigeminal nerve neurons directly accessthe brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase theresidence time of intranasal material, favoring the nose-to-brain delivery. In this first approach,brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA)complexedwith poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-formingmucoadhesive gels, was determined.Materials: 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesivegels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan(1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel releaseprofile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation wasintranasally administered to rats, and blood absorption and brain distribution of radioactivitywere measured.Results: The gelation temperature of both formulations was 23°C. The PxChi liquid showednon-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and thegel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonianbehavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscositysimilar to that of the mucus but higher than that of aqueous solution. The gel released35% of radiolabel and the released material showed silencing activity in vitro. Three intranasaldoses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of32P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel,and administration of two intranasal doses was necessary to achieve higher brain radioactivitythan that achieved by intravenous dendriplexes or intranasal naked siRNA.Conclusion: The increased radioactivity within the olfactory bulb suggested that thecombinationabove mentioned favored the mediation of a direct brain delivery.