Chitosan Nanoparticles

International Journal of Pharmaceutics 250 (2003) 215 Á/226 www.elsevier.com/locate/ijpharm

Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles
Yongmei Xu, Yumin Du 1
Department of Environmental Science, Wuhan University, Wuhan 430072, PR China Received 8 June 2002; received in revised form 15 September 2002; accepted 30 September 2002Abstract Chitosan nanoparticles (CS NP) with various formations were produced based on ionic gelation process of tripolyphosphate (TPP) and chitosan. They were examined with diameter 20 Á/200 nm and spherical shape using TEM. FTIR confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. Factors affecting delivery properties of bovine serum albumin (BSA) asmodel protein have been tested, they included molecular weight (Mw) and deacetylation degree (DD) of chitosan, the concentration of chitosan and initial BSA, and the presence of polyethylene glycol (PEG) in encapsulation medium. Increasing Mws of chitosan from 10 to 210 kDa, BSA encapsulation efficiency was enhanced about two times, BSA total release in PBS (phosphate buffer saline) pH 7.4 in 8days was reduced from 73.9 to 17.6%. Increasing DD from 75.5 to 92% promoted slightly the encapsulation efficiency and decelerated the release rate. The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles. Adding PEG hindered the BSA encapsulation and accelerated the releaserate. # 2002 Elsevier Science B.V. All rights reserved.
Keywords: Chitosan; Bovine serum albumin (BSA); Nanoparticles

1. Introduction The hydrophilic nanoparticles have received much attention to deliver therapeutic peptide, protein, antigen, oligonucleotide and gene by intravenous, oral, and mucosal administration (Janes et al., 2001a). The information has emphasized the importance of size,and revealed the

1 Corresponding author. Tel.: '/86-27-8768-6402; fax: '/8627-8768-6402 E-mail address: duyumin@whu.edu.cn (Y. Du).

advantages of nanoparticles over the microspheres (Meclean et al., 1998), it has been observed that the number of nanoparticles that cross the epithelium is greater than the number of microspheres. Chitosan is a biodegradable and bioadhesive polysaccharide. Ithas been shown that chitosan is non-toxic and soft tissue compatible in a range of toxicity tests (Aspden et al., 1997). It has been widely used in pharmaceutical research and in industry as a carrier for drug delivery and as biomedical material (Mao et al., 2001). Chitosan was selected for nanoparticles because of its recognized mucoadhesivity and ability to enhance

0378-5173/02/$ - see frontmatter # 2002 Elsevier Science B.V. All rights reserved. PII: S 0 3 7 8 - 5 1 7 3 ( 0 2 ) 0 0 5 4 8 - 3

216

Y. Xu, Y. Du / International Journal of Pharmaceutics 250 (2003) 215 Á/226

the penetration of large molecules across mucosal surface (Illum, 1998). More recently, researches have attempted to study chitosan nanoparticles as follows: preparation, modification, properties of loadingvarious drugs and their physiological characters, such as chitosan nanoparticles coated PLGA (Vila et al., 2002) and PEO-PPO (Calvo et al., 1997), nanoparticles loaded insulin (Fernandez-Urrusuno et al., 1999), DNA (Mao et al., 2001) and anticancer drug doxorubicin (Janes et al., 2001b). But some important factors affecting drug properties have not always been investigated, such as basic molecularparameters of chitosan, molecular weight (Mw) and deacetylation degree (DD), were seldom evaluated in protein delivery system of nanoparticles. Janes stated the Mws of chitosan might have a role in the protein or peptide release in the review about chitosan nanoparticles as delivery systems for macromolecules (Janes et al., 2001a), but the relative paper has not been reported. The introduction...