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 (in fungal cell walls and crustacean shells, for example), chitosan is a fully biodegradable and biocompatible and can be used as an adhesive and as an antibacterial and antifungal agent.
Chitosan has been investigated extensively as a potential drug carrier because of its biocompatible properties. Some studies have suggested using chitosan to coat nanoparticles made of other materials to reduce their impact on the body and increase their bioavailability.
The degree of deacetylation and the molecular weight of chitosan can be modified to obtain different physicomechanical 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 ~5.3 x 105 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 has been investigated extensively as a potential drug carrier because of its biocompatible properties. Some studies have suggested using chitosan to coat nanoparticles made of other materials to reduce their impact on the body and increase their bioavailability.
The degree of deacetylation and the molecular weight of chitosan can be modified to obtain different physicomechanical 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 ~5.3 x 105 Daltons.
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 produce chitosan-TPP nanoparticles of sufficient quality for use in clinical applications. The researchers also determined the effect of certain manufacturing parameters on the particle properties, to ensure repeatable results from the production process.
Research carried out 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-hour 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 the 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.
For drug delivery via non-injection to mucosal sites, one of the key challenges is the absorption of the drugs at these sites. The drug delivery system should have mucoadhesive particles and release the drug over time.
Due to the positive charge of chitosan, it can bind with the negatively charged mucus. Thus, chitosan can act as an excellent carrier for mucoadhesive drugs. Chitosan-based nanoparticles have been used to deliver drugs to the lungs, with chitosan helping to attach to the lung mucosa.
Dry powder inhalation of rifampicin, an anti-tuberculer drug, formulated with chitosan as the polymer carrier showed sustained drug release for 24 hours. Similarly, the pulmonary deposition of itraconazole, an anti-fungal drug, increased when formulated as spray-dried microparticles of itraconazole loaded with chitosan nanoparticles.
Gold-Chitosan Particles for Heavy Metal Sensing
In another piece of research in 2005, an innovative strategy for using gold nanoparticles capped with chitosan for sensing heavy metal ions was suggested. Chitosan is polycationic and can therefore be attached to the negatively charged gold nanoparticle surfaces through electrostatic interactions.
Using chitosan provides enough steric hindrance to ensure colloid stability and functionalizing nanoparticles that can be used as sensors. Chitosan’s chelating properties and gold nanoparticles’ optical properties have been used to detect low concentrations of heavy metal ions in water.
Chitosan Particles for Water Treatment
Apart from medical applications, chitosan has also been used in water treatment. The presence of functional groups such as hydroxyl and amino in chitosan make it an excellent adsorbent. One study reported that chitosan-coated nanoparticle membranes were able to remove bacteria much better than uncoated membranes.
Another study in 2015 reported the use of chitosan-zinc oxide nanoparticles for the removal of about 99% color from textile effluent. If the chitosan is made magnetic, it, along with the adsorbed dyes, can easily be recovered using magnetic forces, allowing good reusability of the water.
Applications of Chitosan Nanoparticles
Applications of chitosan nanoparticles are listed below:
- Antibacterial agents, gene delivery vectors and carriers for protein release and drugs.
- A potential adjuvant for vaccines such as influenza, hepatitis B and piglet paratyphoid vaccine.
- 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.
- 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 to enable wound healing.
- The nanoparticles have also been proven to show skin regenerative properties when materials were tested on skin cell fibroblasts and keratinocytes in the laboratory, paving the way to anti-ageing skincare products.
Sources and Further Reading
This article was updated on the 2nd September, 2019.