Influence of Chitosan Glutamate on the in vivo Intranasal Absorption of Rokitamycin from Microspheres

Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries

“…This phenomenon can be attributed to the highly porous structures observed in the CP sample, which allows a faster dissolution of UDCA-AZT with respect to its fragments included in MIX. Moreover, as demonstrated previously by Gavini et al (2011), water soluble chitosans, such as salts, are more able to completely amorphize 24 poorly soluble drugs into the polymer matrix compared to the chitosan base; as a consequence, the dissolution rate and bioavailability of poorly soluble drugs improve.…”

“…Chitosan is poorly soluble in water at physiologic pH values, but it forms salts with inorganic or organic acids, such as hydrochloride and glutamic acid, that are soluble in water and possess better characteristics than chitosan itself, such as mucoadhesiveness and the ability to enhance the penetration of neuroactive agents into the CNS (Dalpiaz et al, 2008;Gavini et al, 2011;Maestrelli et al, 2004). Chitosan is also characterized by the ability to reversibly open tight junctions, which is associated with a potential increase in the transcellular transport of drugs across the olfactory mucosa (Durhia et al, 2010).…”

“…In contrast, the nasal administration of this prodrug appears promising for achieving uptake into the CNS and particularly the CSF. We demonstrated that the nasal administration of chitosan-based microparticles can induce the selective uptake of neuroactive agents into the CSF of rats, probably by promoting drug permeation across the olfactory nasal mucosa (Dalpiaz et al, 2008;Gavini et al, 2011;Rassu et al, 2015a). Very recently, the poor water solubility of UDCA-AZT encouraged us to encapsulate this prodrug in solid lipid microparticles (Dalpiaz et al, 2014).…”

In vitro dissolution/release methods for mucosal delivery systems

“…Basket apparatus (Apparatus 1; Figure 1) has been applied for the in vitro release testing of different mucosal delivery systems, such as nasal microparticles [24] and inserts [25] using relatively large volume (200-400 ml) of the dissolution medium and moderate stirring rate (50 rpm). Similar apparatus, operating with 250 ml of the simulated saliva and 50 or 100 rpm stirring rate were used to investigate the release of tizanidine hydrochloride [26] and buspirone hydrochloride [27] from freeze-dried buccal sponges/wafers.…”

Quantitative determination of zolmitriptan in rat blood and cerebrospinal fluid by reversed phase HPLC–ESI-MS/MS analysis: Application to in vivo preclinical pharmacokinetic study

“…The ability of mucoadesive microemulsions and micellar nanocarriers to enhance the delivery of zolmitriptan to the brain has been preliminarily studied by using radiolabeled drugs, following their administration to rats [6,8]. On the other hand, the potential ability of chitosan microparticles [7] to deliver zolmitriptan to the brain can be hypothesized by considering their demonstrated efficacy in promoting the rat nose-to-brain transfer of anti-ischemic and antibiotic drugs [9,10]. Nevertheless, this hypothesis remains to be validated in preclinical studies and pharmacokinetic data of drug distribution in cerebrospinal fluid (CSF) are required.…”