Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating
- PDF / 3,364,617 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 44 Downloads / 180 Views
ORIGINAL ARTICLE
Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating Edilson Ribeiro de Oliveira Junior 1 & Lílian Cristina Rosa Santos 1 & Mariana Arraes Salomão 1 & Thais Leite Nascimento 1 & Gerlon de Almeida Ribeiro Oliveira 2 & Luciano Morais Lião 2 & Eliana Martins Lima 1
# Controlled Release Society 2020
Abstract Intranasal administration of mucus-penetrating nanoparticles is an emerging trend to increase drug delivery to the brain. In order to overcome rapid nasal mucociliary clearance, low epithelial permeation, and local enzymatic degradation, we investigated the influence of PEGylation on nose-to-brain delivery of polycaprolactone (PCL) nanoparticles (PCL-NPs) encapsulating bexarotene, a potential neuroprotective compound. PEGylation with 1, 3, 5, and 10% PCL-PEG did not affect particle diameter or morphology. Upon incubation with artificial nasal mucus, only 5 and 10% of PCL-PEG coating were able to ensure NP stability and homogeneity in mucus. Rapid mucus-penetrating ability was observed for 98.8% of PCL-PEG5% NPs and for 99.5% of PCL-PEG10% NPs. Conversely, the motion of non-modified PCL-NPs was markedly slower. Fluorescence microscopy showed that the presence of PEG on NP surface did not reduce their uptake by RMPI 2650 cells. Fluorescence tomography images evidenced higher translocation into the brain for PCL-PEG5% NPs. Bexarotene loaded into PCL-PEG5% NPs resulted in area under the curve in the brain (AUCbrain) 3 and 2-fold higher than that for the drug dispersion and for non-PEGylated NPs (p < 0.05), indicating that approximately 4% of the dose was directly delivered to the brain. Combined, these results indicate that PEGylation of PCL-NPs with PCL-PEG5% is able to reduce NP interactions with the mucus, leading to a more efficient drug delivery to the brain following intranasal administration. Keywords Mucus penetration . Polycaprolactone . Fluorescence tomography . Bexarotene . PEGylation . Nose-to-brain delivery
Introduction The design and development of new drug therapies to treat neurological diseases is a hard task [1]. The blood-brain barrier (BBB) is a discerning membrane that regulates the entry of molecules into the central nervous system (CNS), avoiding the permeation of toxic or harmful substances from the systemic circulation into the brain [2]. This protection is very important for the CNS homeostasis; however, it also contributes to poor accumulation of drugs in the cerebral tissue [3]. Consequently, many compounds have been discarded during
* Eliana Martins Lima [email protected] 1
FarmaTec - Centro de PD&I de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Goiás – UFG, 5ª Avenida c/Rua 240 s/n, Praça Universitária, Goiânia, GO 74605-170, Brazil
2
LabRMN, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
clinical studies when administered orally or systemically, since only sub-therapeutic concentrations reach the brain [4]. In an attempt to overcome the aforementioned drawbacks, intra
Data Loading...
