Chitosans administration routes

In this paper after explaining why particulate systems are preferred for vaccine delivery, a brief introduction to chitosan will be given, and the importance of chitosan in particulate systems for vaccine delivery will be emphasized according to administration routes, particularly focused on needle-free routes including, oral, mucosal and pulmonary mucosa as well as skin. For comparison, examples on parenteral route will also be mentioned. 

In the following sections, the application of chitosan-based particulate systems for vaccine delivery will be reviewed according to the administration routes (mucosal, dermal and parenteral) after giving a brief introduction to each route. 

An alternative to the pulmonary route of administration is the nasal route, which is less demanding when it comes to formulation. With regard to, for example, particle size and simpler device development (5,90), examples are Minirin (Ferring), desmopression, and Suprecur (Sanofi-Aventis), buserelin, which are proteins formulated as nasal drops or nasal spray, where bioavailabdities of approximately 3% to 10% can be obtained. The formulations are just protein dissolved in purified water containing preservatives chlorbutanol and benzalkonium chloride (91,92). However, more advanced delivery systems are also used, for example, chitosan formulations where bioavailabihties of 14% to 15% compared to subcutaneous administration can be obtained (90). A recent review by nium (2007) gives more details on nanoparticulate systems used for nasal delivery (93) or consult Costantino et al. (2007) on the physiochemical and therapeutic aspects (5). 

Lipid delivery vehicles such as stealth liposomes [111] and cationic liposome formulations [112-114], and additional vehicles such as polymers of chitosan [115], are being pursued as potential means to improve uptake and distribution of ASOs. Although these novel formulations and alternative routes of administration might ultimately prove to be more successful, the intravenous route has been the most successful thus far in the development of therapeutic ASOs. 

In another interesting report, Jiang et al. showed the successful liver transfection after IP administration of galactosylated chitosan-graft-PEI (GC-g-PEI). Significant GFP expression was observed after IP administration of the polyplexes prepared from GC-g-PEI which was in agreement with the results of the successful in vivo biodistribution using Tc-GC-g-PEI by the same route of administration." Apart from successful DNA delivery by injectable carriers. 

Bivas-Benita et al. (2004) has proposed chitosan-DNA nanoparticles for pulmonary delivery of a DNA vaccine for Mycobacterium tuberculosis. The authors used an HLA-A2 transgenic mouse model to investigate the effect of pulmonary delivery of a new pDNA encoding eight HLA-A 0201-restricted T cell epitopes from M. tuberculosis formulated in chitosan nanoparticles. Pulmonary administration of these nanoparticles was shown to induce the maturation of dendritic cells as well as induce increased levels of IFN-y secretion compared to pulmonary delivery of plasmids in solution or the intramuscular immunization route (Bivas-Benita et al. 2004). 

Oral DNA-based immunotherapy which is a new treatment option for fish inununization in intensive culture to prevent from lymphocystis disease has been reported to have some limitations. Due to the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured when given orally. Chitosan microspheres (<10pm) that contained about twice the amount of pDNA that is generally given to fish by injection route were shown to result in significant pDNA expression in fish after oral administration (Tian et al. 2008) In comparison to immunization via injection with naked pDNA, oral administration of chitosan microspheres loaded with pDNA vaccine were reported to be more stable and last longer for the immunization of fish. 

Sr. No. Route of administration Formulation system Drug incorporated Property imparted by chitosan to the delivery system Reference... 

Mucoadhesive drug delivery systems are comprised of administration of drug across the mucosal membrane using a mucoadhesive/bioadhesive polymer through various noninvasive routes such as peroral, ocular, buccal, nasal, stomach, intestinal, colon, vaginal, rectal, cervical or vulval. The drug delivery systems, which have made use of chitosan as a carrier for administration through various routes, have been represented in Table 2.2. 

Chitosan has also been found to be beneficial in formulation development of delivery systems for local or systemic administration of drug through the rectal route. Chitosan microspheres encapsulating diclofenac sodium incorporated in hydrogels have been designed for efficient rectal administration [126]. Quaternized derivative of chitosan. 

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