Realization of polyaspartamide-based nanoparticles and in vivo lung biodistribution evaluation of a loaded glucocorticoid after aerosolization in mice.
In this study, novel polymeric nanoparticles (NPs) were developed and their potential as carriers for beclomethasone dipropionate (BDP) into the lung after aerosolization was demonstrated by in vivo studies in mice. In particular, these NPs were obtained starting from two polyaspartamide-based copolymers which were synthesized by chemical reaction of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) and its pegylated derivative (PHEA-PEG2000) with poly(lactic acid) (PLA). To obtain nanosized particles, the high pressure homogenization (HPH)-solvent evaporation method was followed by using an organic phase containing both PHEA-PLA and PHEA-PEG2000-PLA (at a weight ratio equal to 1:1), lactose as cryoprotectant and no surfactant was adopted. PHEA-PLA/PHEA-PEG2000-PLA NPs were characterized by a quite spherical shape, ζ potential slightly negative, and size lower than 50 and 200nm, respectively, for empty and BDP-loaded NPs. In vivo biodistribution of BDP and its metabolites in various lung compartments, i.e. bronchoalveolar lavage fluid (BALF), alveolar macrophages (MPG) obtained from BALF, and lung tissue, was carried out at 3h post-administration in mice by aerosolization of BDP-loaded NPs or free BDP (commercial formulation, Clenil(®)) at the dose of 0.5mg/kg BDP. Results demonstrated that BDP entrapped into NPs reached all analyzed lung compartments and were internalized by both alveolar MPG and respiratory epithelial cells, and detected amounts were comparable to those of Clenil-treated mice. Moreover, the entrapment into NPs protects the drug from the enzymatic hydrolysis, allowing a significant lower amount of beclomethasone (BOH) into the lung tissue and BALF than that obtained after Clenil administration.
Department of Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF) Laboratory of Biocompatible Polymers, University of Palermo, Via Archirafi, 32, 90129 Palermo, Italy.
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Craparo
Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
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Di Gioia
Department of Pharmacy, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
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Trapani
Department of Pharmacy, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
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Cellamare
Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
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Belgiovine
Department of Pharmacy, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
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Mandracchia
Department of Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF) Laboratory of Biocompatible Polymers, University of Palermo, Via Archirafi, 32, 90129 Palermo, Italy; IBF-CNR, 90143 Palermo, Italy.
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Giammona
Department of Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF) Laboratory of Biocompatible Polymers, University of Palermo, Via Archirafi, 32, 90129 Palermo, Italy. Electronic address: gennara.cavallaro@unipa.it.
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Cavallaro
Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
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Conese
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001507:Beclomethasone / Q000008:administration & dosage / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D000336:Aerosols; D005938:Glucocorticoids; D010455:Peptides; C017645:polyaspartate; D001507:Beclomethasone
Beclomethasone dipropionate (BDP); Polyhydroxyethylaspartamide; Polymeric nanoparticles