|Abstract: ||The purpose of this study was to develop positively charged nanoparticles (NPs) based on trimethyl chitosan (TMC) and sodium alginate (SA) as drug delivery systems able to interact with the sialic residues of the mucous membranes. The TMC has been synthesised in our laboratory slightly modifying literature procedure, and characterised by 1H-NMR spectroscopy. NPs were prepared with the ionotropic gelation method, using sodium tripolyphosphate (TPP) as cross-linking agent. Ten different nanoparticle formulations were developed by varying the concentration of one component, while keeping constant the other two, or by varying the ratio between the components. The aim of this formulation study was to determine the effect of both polymers and cross-linker concentrations and their ratios on nanoparticle dimensional parameters, such as mean size, size distribution, and surface charge. Overall results of the formulation study indicated that samples prepared with 2 mg/mL TMC concentration and different SA concentrations, namely 1 or 2 mg/mL, showed the best dimensional features, while the optimum concentration of cross-linking agent was 1 mg/mL. Moreover, nanoparticles showed a positive charge surface, suitable to interact with mucous membranes. Preliminary morphological examination of NPs was performed by scanning electron microscopy (SEM), and the interactions between polymers were examined by FTIR and 1H-NMR spectroscopy.
The formulations which show best results in terms of size, size distribution, and surface charge have been used for the encapsulation of two model drugs for
nose to brain drug delivery, progesterone (PG-NPs) and levodopa (LD-NPs), at different concentrations. Indeed, recent developments have proved the possibility of using the nasal pathway for direct transport of drugs from nose to brain. Both PG-NPs and LD-NPs have positive zeta potential (~ + 30 mV) and particle size dependent on the drug concentration. Encapsulation efficiency (EE%) has been calculated for both series, and the obtained data demonstrated that the average EE% values are ranging around 85-90% for PG-NPs and less than 20% for LD-NPs. Therefore, the studied drug delivery system seems to be more suitable for the encapsulation of lipophilic drugs (as PG) than hydrophilic drugs (as LD). We deeper characterised PG-NPs, in terms of stability and drug release profile. We found out that the release of the drug is constant and prolonged and that NPs are almost stable in solution for a 30-day period.
In conclusion, this study reports on the preliminary results on TMC/SA NPs that could represent a promising strategy for nose to brain drug delivery. Further studies are required to confirm the potentiality of these systems, as cytotoxicity and ex-vivo permeation studies, and to evaluate their efficacy in vivo.|