Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(<I>ε</I>-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine

Abstract

Nose-to-brain drug delivery has been proposed to overcome the low absorption of drugs in central nervous system due to the absence of brain-blood barrier in the olfactory nerve pathway. However, the presence of a mucus layer and quick clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules were proposed as a mucoadhesive system to deliver olanzapine after intranasal administration. In vitro evaluations showed that these nanocapsules were able to interact with mucin (up to 17% of increment in particle size and 30% of reduction of particle concentration) and nasal mucosa (2-fold higher force for detaching), as well as to increase the retention of olanzapine (about 40%) on the nasal mucosa after continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer-functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats (1.5-fold higher compared to the drug solution). In accordance with this finding, this formulation improved the prepulse inhibition impairment induced by apomorphine, which is considered as an operational measure of pre-attentive sensorimotor gating impairment present in schizophrenia. Besides, nanoencapsulated olanzapine did not affect the nasal mucosa integrity after repeated doses. These data evidenced that the designed nanocapsules are a promising mucoadhesive system for nose-to-brain delivery of drugs.

Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting

“…Another approach was proposed by the group of Silvia Guterres and Adriana Pohlmann, who developed amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules as a mucoadhesive system for N2B delivery of olanzapine, an atypical antipsychotic drug [ 88 ]. Nanocapsules showed pH-dependent size and surface charge values, ranging from 324.3 to 235.2 nm and from +55 and +22.7 mV.…”

“…Furthermore, the amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules loaded with olanzapine outperformed the controls (drug solution and blank nanocapsules) also in the pre-pulse inhibition model of cognitive impairment symptoms typical of schizophrenia. Interestingly, the authors noted that brain accumulation was higher than that reported in the literature for olanzapine-loaded PLGA nanoparticles and attributed such improvement to the cationic mucoadhesive coating of the nanocapsules [ 88 ].…”

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

“…The mucoadhesive properties of the formulations were assessed using mucin from porcine stomach (Type II, Sigma-Aldrich, St. Louis, MO, USA) as previously described [29,50]. The mucin was dispersed in ultrapure water (0.5% w/v) and employing magnetic stirring for 3 h at room temperature.…”

Preparation and characterization of lamotrigine containing nanocapsules for nasal administration

“…As the nose is a great alternative administration route to allocate APIs directly into the CNS and provides great possibilty to take advantage of NCs, we envisage that a novel, NC formulation made with a bottom-up method could improve the interaction between the drug and the nasal epithelium. Thus the advantages of the nasal delivery and NCs could be combined [19,[51][52][53]. Therefore, the aims of this study were to design and prepare LAM-loaded chitosan NC formulations for nasal drug delivery.…”