Chitosan is an interesting polymer that has been used extensively in the medical field. It is either partially or fully deacetylated chitin. As chitin occurs naturally (for example in fungal cell walls and crustacean shells), chitosan is a fully biodegradable and biocompatible natural polymer, and can be used as an adhesive and as an antibacterial and antifungal agent.
Chitosan has been investigated extensively as a potential drug carrier, due to it's biocompatible properties. Some studies have suggested using chitosan to coat nanoparticles made of other materials, in order to reduce their impact on the body and increase their bioavailability.
The degree of deacetylation and the molecular weight of chitosan can be modified in order to obtain different physico-mechanical properties. The elemental composition of the chitosan polymer is carbon (44.11%), hydrogen (6.84%) and nitrogen (7.97 %). The viscosity average molecular weight of chitosan is ~5.3x105 Daltons.
Scanning electron micrograph of chitosan-coated nanoparticles loaded with docetaxel. Image Credits: S Saremi, Tehran University of Medical Sciences via Open-i, US National Library of Medicine.
Formation of Chitosan Nanoparticles
Chitosan is soluble in acidic conditions - in solution the free amino groups on its polymeric chains can protonate, giving it a positive charge. Chitosan nanoparticles can be formed by incorporating a polyanion such as tripolyphosphate (TPP) into a chitosan solution under constant stirring.
These nanoparticles can then be used for drug delivery and gene therapy applications. Due to its poor solubility at pH more than 6.5, a number of chemically modified chitosan derivatives with improved water solubility can be used as well.
Antifungal Properties of Chitosan
In its free polymer form, chitosan exhibits antifungal activity against Alternaria alternata, Rhizopus oryzae, Aspergillus niger, Phomopsis asparagi, and Rhizopus stolonifer. The antifungal activity of chitosan depends on its concentration, molecular weight, degree of substitution, and the type of functional groups added to the chitosan, as well as the type of fungus.
Whilst derivatives of the polymer can be created to target specific pathogens, chitosan shows natural antifungal activity without the need for chemical modification.
Chitosan Nanoparticles in Drug Delivery
Several research groups have studied the properties of chitosan nanoparticles with a view to using them as a drug delivery agent. The biocompatibility and non-toxicity of the material makes it attractive as a neutral agent for delivery of active agents.
Research in 2005 confirmed that ionic gelation can be used to product chitosan-TPP nanoparticles of sufficient quality for use in clinical applications. The researchers also determined the effect ofcertain manufacturing parameters on the particle properties, to ensure repeatable results from the production process.
Research done in 2006 then focused on the in vitro and in vivo interaction of chitosan nanoparticles (CSNPs), as a new particulate drug carrier, having epithelial cells on the ocular surface. Ionotropic gelation was used to produce the CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin.
Three different CSNP concentrations were taken and human conjunctival epithelial cells (IOBA-NHC) were exposed to them for 15, 30, 60, and 120 minutes. Viability and cell survival were measured after a 24-h recovery period in the culture medium and immediately after treatment.
Confocal microscopy was used to measure the relationship between CSNPs and IOBA-NHC cells. Fluorometry was used to study the impact of temperature and metabolic inhibition. The acute tolerance and the in vivo uptake of the ocular surface to CNSPs were studied in rabbits.
It was observed that uptake of CSNPs was continuous during the time of the experiment and was dependent on temperature. There was no impact on CNSP uptake due to metabolic inhibition by sodium azide.
There were no signs of alteration or inflammation after CSNP exposure on the rabbit’s ocular surface. Fluorescence microscopy of lid sections and rabbit eyeball confirmed in vivo uptake by corneal and conjunctival epithelia. These nanoparticles were well-accepted by the ocular surface tissues.
Gold-Chitosan Particles for Heavy Metal Sensing
In another pice of research in 2005, an innovative strategy for using gold nanoparticles capped with chitosan for sensing heavy metal ions was suggested. Chitosan is polycationic in nature due to which the polymer can be attached to the negatively charged gold nanoparticle surfaces through electrostatic interactions.
Using chitosan enables providing enough steric hindrance ensuring colloid stability and functionalizing nanoparticles to be used as sensors. Chitosan’s chelating properties and gold nanoparticles’ optical properties have been used to detect low concentration of heavy metal ions in water.
Applications of Chitosan Nanoparticles
The applications of chitosan nanoparticles are:
- As antibacterial agents, gene delivery vectors and carriers for protein release and drugs
Used as a potential adjuvant for vaccines such as influenza, hepatitis B and piglet paratyphoid vaccine
Used as a novel nasal delivery system for vaccines. These nanoparticles improve antigen uptake by mucosal lymphoid tissues and induce strong immune responses against antigens.
Chitosan has also been proved to prevent infection in wounds and quicken the wound-healing process by enhancing the growth of skin cells.
Chitosan nanoparticles can be used for preservative purposes while packaging foods and in dentistry to eliminate caries.
It can also be used as an additive in antimicrobial textiles for producing clothes for healthcare and other professionals.
Chitosan nanoparticles show effective antimicrobial activity against Staphylococcus saprophyticus and Escherichia coli.
These materials can also be used as a wound-healing material for the prevention of opportunistic infection and for enabling wound healing.
The nanoparticles have also been proven to show skin regenerative properties when materials were tested on skin cell fibrocblasts and keratinocytes in the laboratory, paving the way to anti-aging skin care products.
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