The nasal delivery of nanoencapsulated statins &amp;ndash; an approach for brain delivery

Clementino, Adryana; Batger, Mellissa; Garrastazu, Gabriela; Pozzoli, Michele; Favero, Elena Del; Rondelli, Valeria; Gutfilen, Bianca; Barboza, Thiago; Sukkar, Maria B.; Souza, Sérgio Augusto Lopes de; Cantù, Laura; Sonvico, Fabio

doi:10.2147/ijn.s119033

Cited by 69 publications

(62 citation statements)

References 79 publications

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“…The identification of the intranasal NCs as a brain delivery approach has been discussed in different studies. For example, Clementino et al [163] reported the NC systems for brain delivery of simvastatin. The drug was loaded in lecithin/chitosan and the system was characterized by a particle size of 200 nm, encapsulation efficiency of 98%, and zeta potential of +48.…”

Section: Nanocapsules (Ncs)mentioning

confidence: 99%

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

Alshweiat

Ambrus

Csóka

2019

CMC

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There is always a need for alternative and efficient methods of drug delivery. The nasal cavity can be considered as a non-invasive and efficient route of administration. It has been used for local, systemic, brain targeting, and vaccination delivery. Although many intranasal products are currently available on the market, the majority is used for local delivery with fewer products available for the other targets. As nanotechnology utilization in drug delivery has rapidly spread out, the nasal delivery has become attractive as a promising approach. Nanoparticulate systems facilitate drug transportation across the mucosal barrier, protect the drug from nasal enzyme degradation, enhance the delivery of vaccines to the lymphoid tissue of the nasal cavity with an adjuvant activity, and offer a way for peptide delivery into the brain and the systemic circulation, in addition to their potential for brain tumor treatment. This review article aims at discussing the potential benefit of the intranasal nanoparticulate systems, including nanosuspensions, lipid and surfactant, and polymer-based nanoparticles as regards productive intranasal delivery. The aim of this review is to focus on the topicalities of nanotechnology applications for intranasal delivery of local, systemic, brain, and vaccination purposes during the last decade, referring to the factors affecting delivery, regulatory aspects, and patient expectations. This review further identifies the benefits of applying the Quality by Design approaches (QbD) in product development. According to the reported studies on nanotechnology-based intranasal delivery, potential attention has been focused on brain targeting and vaccine delivery with promising outcomes. Despite the significant research effort in this field, nanoparticle-based products for intranasal delivery are not available. Thus, further efforts are required to promote the introduction of intranasal nanoparticulate products that can meet the requirements of regulatory affairs with high patient acceptance.

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Section: Nanocapsules (Ncs)mentioning

confidence: 99%

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

Alshweiat

Ambrus

Csóka

2019

CMC

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“…The SVT quantification was carried out by high performance liquid chromatography with detection in the ultraviolet (HPLC-UV), using a previously validated method [30]. The analysis was performed with a Shimadzu HPLC system (Kyoto, Japan) with detection at 238 nm and using a column Phenomenex Lichrosphere ® C18 (4.6.x250 mm, 5 µm).…”

Section: Drug Content and Encapsulation Efficiencymentioning

confidence: 99%

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

Bruinsmann¹,

Pigana²,

Aguirre³

et al. 2019

Preprint

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Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

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“…In vivo studies have shown that after intranasal administration of simvastatin-loaded SACPNs, the 25% of delivered simvastatin can be distributed in the brain and the kidney, with few distribution in other tissues; while for the simvastatin suspension, the drug is mainly distributed in the lung, liver and kidney, but is rarely distributed in the brain, as demonstrated by the plots in Figure 8(b). The results demonstrate that the SACPNs overcome the blood-brain barrier and significantly increase the distribution of the drug in the brain through the nasal cavity to the brain, with good biocompatibility and cytocompatibility (Clementino et al, 2016). Reproduced with permission (Chhonker et al, 2015).…”

Section: Mucosal Deliverymentioning

confidence: 95%

“…Ever since the SACPNs were proposed and fabricated, the applications of SACPNs in drug delivery systems have been extensively studied. Various active pharmaceutical ingredients (APIs) have been encapsulated with optimized encapsulation efficiency, drug loading, particle sizes and unique characteristics, as summarized in Table 2 (Hafner et al, 2011;Barbieri et al, 2013;Chhonker et al, 2015;Moreno et al, 2015;Clementino, Batger, et al, 2016;Clementino, Pozzoli, et al 2018;Alkholief, 2019;Khan, 2019; Terr on-Mej ıa et al, 2018). Due to the remarkable biocompatible and biodegradable of SACPNs, it can be used as ideal drug vehicles for transdermal, mucosal, ocular and oral drug delivery.…”

Section: Advanced Drug Delivery Systemsmentioning

confidence: 99%