Journal of Ocean University of China (Oceanic and Coastal Sea Research) Review

ISSN 1672-5182, July 30, 2007, Vol.6, No.3, pp.237-243

http://www.ouc.edu.cn/xbywb/
E-mail:xbywb@ouc.edu.cn

Preparations, Characterizations and Applications of

Chitosan-based Nanoparticles
LIU Chenguang*, TAN Yulong, LIU Chengsheng, CHEN Xiguang, and YU Lejun

College of Marine Life Science, Ocean University of China, Qingdao 266003, P. R. China

(Received April 17, 2006; accepted November 29, 2006)

Abstract Chitosan is a natural polysaccharide prepared by the N-deacetylation of chitin. In this paper we have reviewed the
methods of preparation of chitosan-based nanoparticles and their pharmaceutical applications. There are five methods of their prepa-
rations: emulsion cross-linking, emulsion-droplet coalescence, ionic gelation, reverse micellar method and chemically modified chi-
tosan method. Chitosan nanoparticles are used as carriers for low molecular weight drug, vaccines and DNA. Releasing characteris-
tics, biodistribution and applications are also summarized.

Key words chitosan; nanoparticle; delivery system

DOI 10.1007/s11802-007-0237-9

All these interesting charactenstics make chitosan an

1 Introduction
Chitin, the second most abundant biopolymer, widely
distributes in nature as the principal component of exo-
skeletons of crustaceans and insects as well as of cell
walls of some bacteria and fungi. It is a glucose-based
unbranched polysaccharide. It differs from cellulose at
the C-2 carbon where an acetamido residue locates in-
stead of a hydroxyl group.
Chitosan is a partially deacetylated polymer of acetyl
glucosamine obtained through alkaline deacetylation of
chitin. It is a compound polymer of glucosamine and
N-acetyl glucosamine. The term chitosan refers to a group
of polymers varying in molecular weight upward to sev-
eral million Daltons (Sevda and McClureb, 2004). The
structure of chitosan is very similar to that of cellulose; it
consists of β(1-4)-linked D-glucosamine residue with
the 2- hydroxyl group being substituted by an amino or
acetylated amino group. The primary amine groups en-
dow chitosan with many special properties, making it
applicable in many areas and readily available for chemi-
cal reactions, for example, salt formation with acids.
Chitosan is positively charged, making it able to adhere to
the negatively charged surface. Chitosan is soluble in
diverse acids and able to interact with polyanions to form
complexes and gels. It holds antibacterial and antifungal
properties. It is safe and nontoxic (Sunil et al., 2004; Se
and Niranjan, 2005).
* Corresponding author. Tel: 0086-532-82032586
E-mail: liucg@ouc.edu.cn
ideal pharmaceutical excipient. It can be used extensively
in drug delivery. A number of studies have been con-
ducted with the aims of using chitosan-based nanoparti-
cles as the carriers of drugs, vaccines and even DNA.
Chitosan-based nanoparticles have provided the opportu-
nities for the site-specific delivery of drugs because they
can solubilize various hydrophobic drugs, increase
bioavailabilty and stay long time in blood circulation sys-
tem. In particular, it has become apparent that, when ad-
ministered systemically, the biocompatible nanoparticles
preferentially accumulate in solid tumors due to their en-
hanced permeability and retention (EPR) effect.
In recent years, for diverse chitosan-based nanoparti-
cles, various methods and different applications have
been developed. In this paper, the major and new find-
ings in the pharmaceutical applications of chitosan-based
nanoparticle drug delivery systems are reviewed, includ-
ing the methods of preparation, drug loading, release
characteristics, biodistribution and idiographic applica-
tions.
2 Methods of Preparing Chitosan Nano-
particles
2.1 Emulsion Cross-linking
A water-oil (w/o) emulsion is prepared by emulsifying
the chitosan aqueous solution in oil (Ohya et al., 1994;
Yokohama et al., 1998; Kataoka et al., 2000). Aqueous
droplets are stabilized using a suitable surfactant. The
stable emulsion is cross-linked by using an appropriate
cross-linking agent such as glutaraldehyde to harden the