Solid microparticles based on chitosan or methyl-β-cyclodextrin: A first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate

Abstract

We propose the formulation and characterization of solid microparticles as nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron like), but like DCH did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial like). Nasal administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) and 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after nasal administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

“…As expected, the inclusion of drugs had no effect on size, given the relatively low loading. Real, bulk and tap densities were also very similar amongst the formulations, with real density varying within 1.3-1.4 g/cm 3 (Table 2), very common values for spray-dried powders [18,25]. Bulk densities varied between 0.14 and 0.25 g/cm 3 and tap densities had slightly increased values in comparison with the former, as a consequence of the method used for the determinations.…”

Encapsulation of l-menthol in hydroxypropyl-β-cyclodextrin and release characteristics of the inclusion complex

“…The inclusion complexes formed by CDs and volatile or unstable molecules can achieve prolonged shelf-life and high temperature stability 9 . Furthermore, CDs possess a special ability to complex with drugs enabling them to increase solubility, reduce bitterness, and decrease tissue irritation upon dosing 10, 11 . Among the numerous CDs and their derivatives, hydroxypropyl-β-cyclodextrin (HP-β-CD) is a hydroxyalkylated cyclodextrin and has been widely used to increase the solubility, stability, and bioavailability of drugs, because it has more water solubility and low toxicity 12, 13 .…”

Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries

“…In general, appropriate strategies are required to improve the brain delivery of drugs, such as the addition of penetration enhancers and mucoadhesive materials to formulations or the preparation of micro-and nano-particulate delivery systems (Casettari and Illum, 2014;Dalpiaz et al, 2008;Horvát et al, 2009;Mistry et al, 2009;Rassu et al, 2015a). In this regard, chitosan is a polysaccharide derived from the alkaline deacetylation of chitin that is used in different formulations for the nose-to-brain delivery of drugs (Casettari and Illum, 2014) due to its biocompatibility, nontoxicity and high charge density, which confers mucoadhesive properties (Bernkop-Schnürch and Dünnhaupt, 2012;Sinha et al, 2004).…”