Chitosan Microspheres as Potential Vaccine Delivery Systems

Authors

  • Saravana Kumar A Pharmaceutical sciences Discipline, Anna University Coimbatore, Academic Campus, Jothipuram - 641047, Tamilnadu, India
  • Ramaswamy NM Pharmaceutical sciences Discipline, Anna University Coimbatore, Academic Campus, Jothipuram - 641047, Tamilnadu, India

Keywords:

Tetanus toxoid, Chitosan microspheres, Vaccine delivery system, Biodegradable polymers

Abstract

The recent advances in controlled delivery systems for protein pharmaceuticals such as microspheres, liposomes, pumps and implants, have provided a new avenue for delivery of vaccine antigens. Adjuvants aimed at increasing the immunogenicity of recombinant antigens remain a focus in vaccine development worldwide, there is currently considerable care for the development of chitosan microspheres as controlled release of vaccines, since the major disadvantage of several currently available vaccines is the need for repeated administration. Microspheres prepared from the biodegradable and biocompatible polymers, chitosan have been shown to be effective adjuvants for a number of antigens. This review mainly focuses on chitosan microspheres adjuvant as vaccine delivery systems by summarizing our and other research groups’ investigation on properties of microspheres formulation encapsulating several kinds of antigens. The results indicate that compared with commonly used PLA and PLGA, chitosan biomaterial has several potentials in vaccine delivery systems. Chitosan microspheres can control the rate of release of entrapped antigens and therefore, offer generation adjuvant to replace or complement existing aluminium salts for vaccine potential. The review mainly aims to promote the investigation of chitosan microspheres adjuvant for antigens for world wide researcher.

References

Plotkin SL, Plotkin SA, in: Plotkin SA,

Mortimer EA Jr. (Eds). A short history of

vaccination and vaccines, Saunders,

Philadelphia, PA, 1988, 1-7.

Shari Lofthouse. Immunological aspects of

controlled antigen delivery. Adv Drug Deli

Rev 2002; 54:863-870.

Men Y, Thomasin C, Merkle HP, Gander B,

Corradin G. A Single administration of

tetanus toxin in biodegradable microspheres

elicits T cell and antibody responses similar

or superior to those obtained with aluminium

hydroxide. Vaccine 1995; 13:683-689.

Warren HS, Vogel FR, Chedid LA. Current

status of immunological adjuvants. Ann Rev

Immunol 1986;4: 369-376.

Kohn J, Niemi SM, Albert EC, Murphy JC,

Langer RS, Fox JG. Single-step

immunization using a controlled release,

biodegradable polymer with sustained

adjuvant activity. J Immunol Methods 1986;

: 31- 37.

Physician’s Desk Reference, 46th ed, Medical

Economics Data. 1992; 1544-1546.

Bittle JL, Murphy FL. Vaccine Biotechnol.

; 33: 313.

Allison AC, Byars NE. Immunological

adjuvants: desirable properties and side

effects. Molec Immunol 1991; 28: 279-283.

Zhao Z, Leong KW. Controlled delivery of

antigens and adjuvants in vaccine

development. J Pharm Sci 1996; 85 (12):

-1270.

Nellore RV, Pande PG, Young D, Bhagat

HR. Evaluation of biodegradable

microspheres as vaccine adjuvant for

Hepatitis B surface antigen. J Parenteral Sci

Tech 1992; 46: 176-180.

Yamaguchi K, Anderson JM. In vivo

biocompatibility studies of medisorb 65/35

D.L-lactide / glycolide copolymer

microspheres. J Control Release 1993; 24: 81-

Aguado MT, Lambert PH. Controlled release

vaccines biodegradable polylactidepolyglycolide (PL / PG) microspheres as

antigen vehicles. Immunobiol 1992;184: 113-

Esparza I, Kissel T. Parameters affecting the

immunogenicity of microencapsulated tetanus

toxoid. Vaccine 1992; 10: 714-720.

Raghuvanshi RS, Singh M, Talwar GP.

Biodegradable delivery system for single step

immunization with tetanus toxoid. Int J

Pharm 1993; 93: R1-R5.

Alonso MJ, Cohen S, Park TG, Gupta RK,

Siber GR, Langer R. Determinants of release

rate of tetanus vaccine from polyester

microspheres. Pharm.Res 1993;10: 945-953.

Alonso MJ, Gupta RK, Min C, Siber GR,

Langer R. Biodegradable microspheres as

controlled-release tetanus toxoid delivery

systems. Vaccine 1994; 12: 299-306.

Change AC, Gupta RK. Stabilization of

tetanus toxoid in poly (D,L,lactide-coglycolic acid) microspheres for the controlled

release of antigen. J Pharm Sci 1996; 85: 129-

Langer R. New methods of drug delivery.

Science 1990; 249: 1527-1533.

Tice TR, Mason DW, Ghley RM. Clinical use

and future of parenteral microspheres delivery

systems, in: F.Prescot, W.S.Nimmo (Eds.),

Drug Delivery and its Therapeutic

Applications, Wiley, London, 1989, Chapter

Wise DL, Fellman TD, Sanderson JE,

Wentworth RL. Lactide / glycolide polymers

used in as surgical suture material, raw

material for osteosynthesis and in sustained

release forms of drugs, in:G.Gregoriadis

(Ed.), Drug Carriers in Medicine, Academic

Press, London. 1979; 237.

Singh M, Li XM, Wang HY, McGee JP,

Zamb T, Koff W, Wang CY, O’Hagan DT.

Immunogenecity and protection in small

animal models with controlled release tetanus

toxoid microparticles as a single-dose

vaccine. Infect Immun 1997;65: 1716-1721.

Illum L. Chitosan and its use as a

pharmaceutical excipient. Pharm Res 1998;

:1326-1331.

Felt O, Buri P, Gurny R. Chitosan: a unique

polysaccharide for drug delivery. Drug Dev

Ind Pharm 1998; 24:979-993.

Joane RJ, Frier M, Perkins AC, Jones NS,

Davis SS, Illum L. Evaluation of the

clearance characteristics of bioadhesive

systems in humans. Int J Pharm 1999;

:55-65.

Vander Lubben LM, Verhoef JC, Borchard G,

Junginger HE. Chitosans for mucosal

vaccination. Adv Drug Deliv Rev

;52:139-144.

Derek T, O’Hagan DT, Rino Rappuoli. Novel

approaches to vaccine delivery.

Pharmaceutical Research 2004; 21(9): 1519-

Valiante NM, O’Hagan DT, Ulmer J. Innate

immunity and biodefense vaccines. Cell

Microbiol 2003; 5:755-760.

Artursson P, Lindmark T, Davis SS, Illum L.

Effect of chitosan on the permeability of

monolayers of intestinal epithelial cells

(Caco-2). Pharm Res 1994; 11:1358–1361.

Borchard G, Luessen HL, De Boer AG,

Verhoef JC, Lehr CM, Junginger HE. The

poteltial of mucoadhesive polymers in

enhancing intestinal peptide drus absorption.

III: Effect of chitosan glutamate and

carbomer on epithelial tight junctions in vitro.

J Control Release 1996; 39:131–138.

Dodane V, Khan MA, Merwin JR. Effect of

chitosan on epithelial permeability and

structure. Int J Pharm 1999; 182:21–32.

Schipper NG, Varum KM, Artursson P.

Chitosans as absorption enhancers for poorly

absorbable drugs. 1: Influence of molecular

weight and degree of acetylation on drug

transport across human intestinal epithelial

(Caco-2) cells. Pharm Res 1996; 13:1686–

Luessen HL, de Leeuw BJ, Langemeyer MW,

de Boer AB, Verhoef JC, Junginger HE.

Mucoadhesive polymers in peroral peptide

drug delivery. VI. Carbomer and chitosan

improve the intestinal absorption of the

peptide drug buserelin in vivo. Pharm Res

; 13:1668–1672.

Jabbal-Gill I, Fisher AN, Rappuoli R, Davis

SS, Illum L. Stimulation of mucosal and

systemic antibody responses against

Bordetella pertussis filamentous

haemagglutinin and recombinant pertussis

toxin after nasal administration with chitosan

in mice. Vaccine 1998; 16:2039–2046.

McNeela EA, O'Connor D, Jabbal-Gill I,

Illum L, Davis SS, Pizza M, et al. A mucosal

vaccine against diphtheria: formulation of

cross reacting material (CRM (197)) of

diphtheria toxin with chitosan enhances local

and systemic antibody and Th2 responses

following nasal delivery. Vaccine 2000;

:1188–1198.

Xie Y, Zhou NJ, Gong YF, Zhou XJ, Chen J,

Hu SJ, et al. Th immune response induced by

H. pylori vaccine with chitosan as adjuvant

and its relation to immune protection. World J

Gastroenterol 2007; 13:1547–1553.

Seferian PG, Martinez ML. Immune

stimulating activity of two new chitosan

containing adjuvant formulations. Vaccine

; 19:661–668.

Soane RJ, Hinchcliffe M, Davis SS, Illum L.

Clearance characteristics of chitosan based

formulations in the sheep nasal cavity. Int J

Pharm 2001;217:183–191.

Desai MP, Labhasetwar V, Walter E, Levy

RJ, Amidon GL. The mechanism of uptake of

biodegradable microparticles in Caco-2 cells

is size dependent. Pharm Res 1997; 14:1568–

Eldridge JH, Staas JK, Meulbroek JA, Tice

TR, Gilley RM. Biodegradable and

biocompatible poly(DL-lactide-co-glycolide)

microspheres as an adjuvant for

staphylococcal enterotoxin B toxoid which

enhances the level of toxin-neutralizing

antibodies. Infect Immun 1991; 59:2978–

O'Hagan DT, Jeffery H, Davis SS. Long-term

antibody responses in mice following

subcutaneous immunization with ovalbumin

entrapped in biodegradable microparticles.

Vaccine 1993a; 11:965–969.

Pereswetoff-Morath L. Microspheres as nasal

drug delivery systems. Adv Drug Deliv Rev

;29:185–194.

Chowdary KP, Rao YS. Mucoadhesive

microspheres for controlled drug delivery.

Biol Pharm Bull 2004;27:1717–1724.

Tian J, Yu J, Sun X. Chitosan microspheres

as candidate plasmid vaccine carrier for oral

immunisation of Japanese flounder

(Paralichthys olivaceus). Vet Immunol

Immunopathol 2008; 126:220–229.

Ahire VJ, Sawant KK, Doshi JB, Ravetkar

SD. Chitosan microparticles as oral delivery

system for tetanus toxoid. Drug Dev Ind

Pharm 2007;33:1112–1124.

Takahiro Nagamoto, Yoshiyuki Hattori, Kozo

Takayama, Yoshie Maitani. Novel chitosan

particles and chitosan-coated emulsions

inducing immune response via intranasal

vaccine delivery. Pharmacological Research,

(4), 671-674 (2004).

Arthanari Saravanakumar, Nachipalayam

Muthusamy Ramaswamy. Formulation and

in-vitro evaluation of tetanus toxoid loaded

chitosan microspheres. J of Pharm Research

; 2(5): 893-896.

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Published

2011-03-31

How to Cite

Saravana Kumar A, & Ramaswamy NM. (2011). Chitosan Microspheres as Potential Vaccine Delivery Systems. International Journal of Drug Delivery, 3(1), 43–50. Retrieved from https://ijdd.arjournals.org/index.php/ijdd/article/view/53

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Section

Review Article