Chitosan-Based Nanoparticles for Targeted Nasal Galantamine Delivery as a Promising Tool in Alzheimer’s Disease Therapy (original) (raw)
Related papers
Intranasal Delivery of Chitosan Nanoparticles for Migraine Therapy
Scientia Pharmaceutica, 2013
Objective: The objective of the research was to formulate and evaluate sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order to improve its therapeutic effect and reduce dosing frequency. Material and Methods: The Taguchi method design of experiments (L9 orthogonal array) was applied to obtain the optimized formulation. The sumatriptan succinateloaded chitosan nanoparticles (CNPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and Tween 80 as surfactant. Results: The CNPs had a mean size of 306.8 ± 3.9 nm, a zeta potential of +28.79 mV, and entrapment efficiency of 75.4 ± 1.1%. The in vitro drug release of chitosan nanoparticles was evaluated in phosphate buffer saline pH 5.5 using goat nasal mucosa and found to be 76.7 ± 1.3% within 28 hours. Discussion: The release of the drug from the nanoparticles was anomalous, showing non-Fickian diffusion indicating that drug release is controlled by more than one process i.e. the superposition of both phenomena, a diffusion-controlled as well as a swelling-controlled release. This is clearly due to the characteristics of chitosan which easily dissolves at low pH, thus a nasal pH range of 5.5 ± 0.5 supports it very well. The mechanism of pH-sensitive swelling involves protonation of the amine groups of chitosan at low pH. This protonation leads to chain repulsion, diffusion of protons and counter ions together with water inside the gel, and the dissociation of secondary interactions. Conclusion: The results suggest that sumatriptan succinate-loaded chitosan nanoparticles are the most suitable mode of drug delivery for promising therapeutic action.
Preparation of Carbamazepine Chitosan Nanoparticles for Improving Nasal Absorption
Journal of Drug Delivery and Therapeutics, 2015
In this study the nasal administration of carbamazepine has been studied using chitosan nanopartcles. The chitosan nanoparticles were prepared by ionic gelation of chitosan (100-300mg) with Tripolyphosphate sod (100-300mg in 100ml. Nine formulations were prepared, characterized and compared in terms of morphology (Transmission electron microscopy), drug content, particle size (zetasizer) and In-vitro drug release. In-vitro drug release studies were performed in Franz diffusion cell using phosphate buffer (buffer pH 5.5) as dissolution medium. The Chitosan nanoparticles had a mean size of 124.2±05 to 580±13nm, zeta potential were found to be +21 to 26.6 mV and the entrapment efficiency were found to be 65 to 72.7%. The in-vivo study was performed on Wistar rat, nanoparticles were administered through nasal route and compared with carbamazepine given by i.v. route, the results indicate that carbamazepine loaded chitosan nanoparticles enhances the drug absorption through nose. The results showed that the carbamazepine could be directly transported into the rat brain through nose and the possible side effects could be minimized.
Olanzapine is an atypical antipsychotic drug shows low bioavailability due to extensive first pass metabolism and results in numerous side effects due to non targeted delivery. The present study was aimed to prepare and characterize olanzapine loaded chitosan nanoparticles for nose to brain targeting. The olanzapine loaded chitosan nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. The formulated nanoparticles showed mean particle size, polydispersity index and zeta potential to be 183.1±8.42 nm, 0.122±0.08, +52.1±2.4 mV respectively. The entrapment efficiency and drug loading was found to be 72.42 ±3.65% and 26 .04± 2.12. In vitro drug release was showed a biphasic release pattern with initial burst release followed by sustained release of formulated nanoparticles. In vitro toxicity studies were carried out on RPMI 2650 human nasal epithelial cell line by MTT assay. The obtained result shows lower toxicity (high IC 50 value) of nanoformulation as compared to free drug. Ex vivo histopathological studies were carried out by using excised goat nasal mucosa and the microscopic structure of nasal mucosa shows no significant harmful effects of formulated nanoparticles. These results illustrate that olanzapine loaded chitosan nanoparticles is a potential new delivery system for treatment of depressant when transported via olfactory nasal pathway to the brain.
Comptes rendus de l’Acad´emie bulgare des Sciences, 2020
Chitosan and alginate are widely applied biopolymers in drug delivery systems. Their use as either micro- and nanoparticulate drug carriers or coating agents has been reviewed. Many surveys have discussed the application of chitosan and alginate as carriers alone. The present review is focused on the nanoparticles prepared only by their electrostatic complexation. The main advantages of chitosan-alginate nanoparticles are discussed, in particular the simple preparation, protection of unstable drugs, bioadhesive properties, low toxicity and possibilities for functionalization, adjusting of surface charge and drug release rate. The specific problems that these nanoparticles could target at oral, nasal and ocular administration are also considered.
Chitosan-Based Nanocarriers for Nose to Brain Delivery
In the treatment of brain diseases, most potent drugs that have been developed exhibit poor therapeutic outcomes resulting from the inability of a therapeutic amount of the drug to reach the brain. These drugs do not exhibit targeted drug delivery mechanisms, resulting in a high concentration of the drugs in vital organs leading to drug toxicity. Chitosan (CS) is a natural-based polymer. It has unique properties such as good biodegradability, biocompatibility, mucoadhesive properties, and it has been approved for biomedical applications. It has been used to develop nanocarriers for brain targeting via intranasal administration. Nanocarriers such as nanoparticles, in situ gels, nanoemulsions, and liposomes have been developed. In vitro and in vivo studies revealed that these nanocarriers exhibited enhanced drug uptake to the brain with reduced side effects resulting from the prolonged contact time of the nanocarriers with the nasal mucosa, the surface charge of the nanocarriers, the nano size of the nanocarriers, and their capability to stretch the tight junctions within the nasal mucosa. The aforementioned unique properties make chitosan a potential material for the development of nanocarriers for targeted drug delivery to the brain. This review will focus on chitosan-based carriers for brain targeting.
Nanotechnology mediated drug delivery has been reported to enhance the drug efficacy, bioavailability, reduce toxicity and improve patient compliance by targeting the cells and tissues to produce desired pharmacological action. Aim: The purpose of the present study was to formulate and evaluate Polysorbate 80 Coated Chitosan Nanoparticles of Rivastigmine for brain delivery. Methods: Rivastigmine is short acting cholinesterase inhibitors (ChEI). Nanostructure mediated drug delivery enhances drug bioavailability, improves the timed release of drug molecules, and enables precision drug targeting. Because of its cationic charges, biocompatibility, and low toxicity, chitosan has been used as a vehicle system for genes, protein and drugs. The Nanoparticles were evaluated for size, shape, zeta potential, microscopy, transmission electron microscopy. Drug-polymer compatibility was determined using differential scanning calorimetry. The amount of drug entrapped within the Nanoparticles was determined spectrofluorometrically and in vitro drug release studies were done by spectrofluorometer. Test was used to evaluate in vivo activity of Rivastigmine Nanoparticles in mice. The drug-loading capacity obtained from the drug content analyses for the batches ranged from 43.48±3.5 to 52.62±4.31 depending upon the drug-to-polymer ratio. The drug loading of chitosan Nanoparticles (drug-to-polymer ratio 1:1) after coating with 1% Polysorbate 80 was 43.48±1.3. The particle size analysis showed that the mean particle size of drug-loaded Nanoparticles (drug-to-polymer ratio 1:1) was 45.16±1.56 nm.
Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery
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 encaps...
Polymers
The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via 1H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS’s utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil–water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release s...
Journal of Controlled Release, 2006
In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of proteins was investigated. TMC nanoparticles were prepared by ionic crosslinking of TMC solution (with or without ovalbumin) with tripolyphosphate, at ambient temperature while stirring. The size, zeta-potential and morphology of the nanoparticles were investigated as a function of the preparation conditions. Protein loading, protein integrity and protein release were studied. The toxicity of the TMC nanoparticles was tested by ciliary beat frequency measurements of chicken embryo trachea and in vitro cytotoxicity assays. The in vivo uptake of FITC-albumin-loaded TMC nanoparticles by nasal epithelia tissue in rats was studied by confocal laser scanning microscopy. The nanoparticles had an average size of about 350 nm and a positive zeta-potential. They showed a loading efficiency up to 95% and a loading capacity up to 50% (w/w). The integrity of the entrapped ovalbumin was preserved. Release studies showed that more than 70% of the protein remained associated with the TMC nanoparticles for at least 3 h on incubation in PBS (pH 7.4) at 37 -C. Cytotoxicity tests with Calu-3 cells showed no toxic effects of the nanoparticles, whereas a partially reversible cilio-inhibiting effect on the ciliary beat frequency of chicken trachea was observed. In vivo uptake studies indicated the transport of FITC-albumin-associated TMC nanoparticles across the nasal mucosa. In conclusion, TMC nanoparticles are a potential new delivery system for transport of proteins through the nasal mucosa. D