Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 259

6.6.1.1 Diffusion-Controlled Mechanism ........................................................ 290
6.6.1.2 Swelling-Controlled Mechanisms ........................................................ 290
6.6.1.3 Chemically Controlled Mechanisms.................................................... 291
6.6.2 Drug Release Stimuli............................................................................................. 291
6.6.2.1 pH-Sensitive Release............................................................................... 292
6.6.2.2 pH and Temperature Dual-Sensitive Release ..................................... 293
6.6.2.3 Electric-Sensitive Release....................................................................... 294
6.6.2.4 Enzyme-Sensitive Release ..................................................................... 295
6.6.2.5 Glucose-Sensitive Release ...................................................................... 295
6.6.3 Targeted Drug Release .......................................................................................... 296
6.6.3.1 Passive Targeting: EPR Effect ................................................................ 296
6.6.3.2 Active Targeting: RME ........................................................................... 298
6.6.3.3 Physical Targeting................................................................................... 299
6.7 Application.......................................................................................................................... 299
6.7.1 Drug Delivery in the Oral Cavity........................................................................ 299
6.7.2 Nasal Drug Delivery ............................................................................................. 300
6.7.3 Gastric Drug Delivery ........................................................................................... 301
6.7.4 Colonic Drug Delivery .......................................................................................... 301
6.7.5 Ocular Drug Delivery ........................................................................................... 302
6.7.6 Transdermal Drug Delivery ................................................................................. 303
6.8 Commercial Products........................................................................................................ 304
6.9 Conclusions......................................................................................................................... 305
References..................................................................................................................................... 306
6.1 Introduction
To date, a large number of active compounds have been discovered that serve as therapeu-
tics for curing complex disease. Yet, very few have shown clinical success. One major chal-
lenge is the delivery of an effective dose of a given cytotoxic agent to the target site without
losing its functionality, while at the same time minimizing unintended harmful side
effects [1]. As is well known, during systemic administration, drugs lose functionality very
soon and the blood plasma concentration of the drug can quickly drop below an effective
level. Readministration is required, leading to an increase in the risk of an overdose.
Another problem is that many medications such as peptide and protein, antibody, vaccine,
and gene-based drugs, in general, may not be delivered using common routes because
they might be susceptible to enzymatic degradation or cannot be absorbed into the sys-
temic circulation efficiently in order to be therapeutically effective, due to molecular size
and charge issues [2].
Under such circumstances, a drug delivery system (DDS) becomes an alternative tech-
nique for improving the pharmacological properties of traditional chemotherapeutics.
Active therapeutics are incorporated into a polymeric network structure, and drug
release profile, absorption, distribution, and elimination are modified in order to improve
product efficacy and safety as well as patient convenience and compliance [3]. According
to the application, the drug is released from a formulation over a period of time from a
few hours to a month to several years in a controlled manner. A large variety of synthetic
and natural polymers have been studied as drug carriers, such as poly(l-lactic acid) and