Core shell methyl methacrylate chitosan nanoparticles: in vitro mucoadhesion and complement activation

Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione [GSH] to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum [HS] by measurement of the hemolytic capacity of the complement system after contact with nanoparticles. The FT-IR and 1HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate [MMA] homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan

Preparation and evaluation of poly [caprolactone fumarate] nanoparticles containing doxorubicin HCl

Biodegradable Poly[caprolactone fumarate] [PCLF] has been used as bioresorbable sutures. In this study, doxorubicin HCl [Dox] loaded PCLF nanoparticles were prepared and characterized. PCLFs were synthesized by polycondensation of PCL diols [Mws of 530, 1250 and 2000] with fumaryl chloride. The degradation of PCLF in NaOH, water and phosphate buffer saline [PBS], was determined in terms of Mw. Nanoparticles [NPs] were prepared by two methods. In microemulsion polymerization method, dichloromethane containing PCLF and photoinitiator were combined with the water containing surfactants and then the mixture was placed under light for crosslinking. In nanoprecipitation method, the organic solvent containing PCLF was poured into the stirring water. The effect of several variables including concentration of PCLF, polyvinyl alcohol [PVA], Dox and Trypan blue [Trb] and the Mw of PCLF and PVA on NP size and loading were evaluated. PCLF 530, 1250 and 2000 in PBS or water were not degraded over 28 days. Nanoprecipitaion method gave spherical [revealed by SEM images] stable NPs of about 225 with narrow size distribution and a zeta potential of-43 mV. The size of NP increased significantly by increase in Mw or concentration of PCLF. Although PVA was not necessary for formation of NPs, but it decreased the NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing the drug concentration, increased the drug loading [DL] and NP size. The entrapment efficiency [EE] for Trb ranged from 1% for PCLF530 to 6% for PCLF2000. An increase in PCLF concentration resulted in an increase in EE. Dox and Trb release showed a burst followed by 80% and 78% release during 3 and 4 days respectively. PCLF possessed suitable characteristics for preparation nanoparticulate drug delivery system including desired NP size, stability and degradation time. Although PCLF530 NPs were the smallest, but their DL were lower than PCLF1250 and 2000 NPs

Preparation and comparison of chitosan nanoparticles with different degrees of glutathione thiolation

Chitosan has gained considerable attentions as a biocompatible carrier to improve delivery of active agents. Application of this vehicle in the form of nanoparticle could profit advantages of nanotechnology to increase efficacy of active agents. The purpose of this study was to provide detailed information about chitosan-glutathione [Cht-GSH]nanoparticles which are gaining popularity because of their high mucoadhesive and extended drug release properties. Depolymerization of chitosan was carried out using sodium nitrite method. Glutathione was covalently attached to chitosan and the solubility of the resulting conjugates was evaluated. Nanoparticles were prepared by ionic gelation method and then the effect of glutathione immobilization on properties of nanoparticles was investigated. Thiolation efficiency was higher in lower molecular weight chitosan polymers compared to unmodified chitosan nanoparticles. Cht-GSH conjugates of the same molecular weight but with different degrees of thiolation had the same hydrodynamic diameter [995 +/- nm] and surface charge [102 +/- mV] as unmodified chitosan, but comprised of a denser network structure and lower concentration. Cht-GSH nanoparticles also exhibited greater mucoadhesive strength which was less affected by ionic strength and pH of the environment. Thiolation improves the solubility of chitosan without any significant changes in size and charge of nanoparticles, but affects the nanogel structure

Aluminum phosphate shows more adjuvanticity than Aluminum hydroxide in recombinant hepatitis-B vaccine formulation

Although a number of investigation have been carried out to find alternative adjuvants to aluminum salts in vaccine formulations, they are still extensively used due to their good track record of safety, low cost and proper adjuvanticity with a variety of antigens. Adsorption of antigens onto aluminum compounds depends heavily on electrostatic forces between adjuvant and antigen. Commercial recombinant protein hepatitis B vaccines containing aluminum hydroxide as adjuvant is facing low induction of immunity in some sections of the vaccinated population. To follow the current global efforts in finding more potent hepatitis B vaccine formulation, adjuvanticity of aluminum phosphate has been compared to aluminum hydroxide. The adjuvant properties of aluminum hydroxide and aluminum phosphate in a vaccine formulation containing a locally manufactured hepatitis B [HBs] surface antigen was evaluated in Balb/C mice. The formulations were administered intra peritoneally [i.p.] and the titers of antibody which was induced after 28 days were determined using ELISA technique. The geometric mean of antibody titer [GMT], seroconversion and seroprotection rates, ED50 and relative potency of different formulations were determined. All the adjuvanicity markers obtained in aluminum phosphate formulation were significantly higher than aluminum hydroxide. The geometric mean of antibody titer of aluminum phosphate was approximately three folds more than aluminum hydroxide. Aluminum phosphate showed more adjuvanticity than aluminum hydroxide in hepatitis B vaccine. Therefore the use of aluminum phosphate as adjuvant in this vaccine may lead to higher immunity with longer duration of effects in vaccinated groups