Biomedical Engineering Reference
In-Depth Information
20.6
TARGETED DRUG DELIVERY WITH BIOMATERIALS
20.6.1 D
RUG
D
ELIVERY
TO
THE
C
OLON
One of the most extensive areas of biomaterials research related to the gastrointestinal tract is
the development of drug delivery devices. Biodegradable particulate carrier systems for oral drug
delivery offer a number of potential benefi ts including enhancement of absorption, bioavailability,
site-specifi c targeting, and a delivery system for oral immunization. This section will focus on the
widely used oral l adm in ist ration route for d r ug deliver y to t The colon. T The colon is a n at t ractive site for
drug delivery due to its less hostile environment compared with upper regions of the gastrointestinal
tract, slower transit times allowing longer drug retention, and richness in gut-associated lymphoid
tissue that facilitates effi cient vaccine delivery. However, the bioavailability of peptide and protein
drugs after oral administration can be low due to their instability in the gastrointestinal tract and
low permeability through the intestinal mucosa. Therefore, a number of strategies have been devel-
oped to deliver intact molecules to the colon, including pH-sensitive coatings, timed-release sys-
tems, mucoadhesive systems, nanoparticles for site-specifi c accumulation, and polymers that are
degraded by colonic bacteria. Many of these colon-targeted drug delivery systems are applied as
coatings to conventional hard gelatin capsules [61].
Timed-release drug delivery systems are based on the principle of delivering drugs after a par-
ticular time, which is usually the time required to reach the colon after gastric emptying (3-4 h).
However, this approach is limited since gastric emptying can vary considerably depending on the
quantity and the type of food consumed and also the well-being of the patient.
The pH conditions of the gastrointestinal tract vary considerably along its length, increas-
ing from acidic in the stomach (pH 1-4) to a neutral/slightly alkaline pH in the distal part of
the small intestine and the colon. Colon targeting using polymer coatings that are pH-sensitive
needs to withstand the acidic conditions of the stomach and proximal part of the small intestine
before disintegrating in the neutral/alkaline pH of the colon. One of the most commonly used pH-
dependent coatings is a copolymer of methacrylic acid and methyl methacrylate, such as Eudragit
(Röhm Pharmaceuticals, Germany).
20.6.1.1
Chitosan-Based Drug Delivery Systems
Chitosan, a naturally occurring polymer, relies on different inherent properties to make it suit-
able for colonic specifi c delivery. These properties include (i) its sensitivity to biodegradation by
lysozyme, an enzyme found highly concentrated in the colonic mucosa, and other colonic bacteria-
derived enzymes and (ii) its mucoadhesive properties [62]. It is, therefore, a particularly attractive
biomaterial because of its nontoxicity, biocompatibility, and biodegradability.
Chitosan is a copolymer of
N
-acetyl-d-glucosamine and d-glucosamine and is derived from
chitin by alkaline deacetylation. Chitin is the second most abundant protein in nature, found
in the exoskeleton of crustaceans, insects, and some fungi. To prepare chitosan, chitin is ini-
tially extracted from the shell of crustaceans by treatment for a few hours with 3-5% (w/v)
NaOH aqueous solution at 80-90°C to remove proteins, followed by treatment with 3-5% (w/v)
aqueous HCl to remove inorganic constituents of the shell. N
-
deacetylation of chitin to pro-
duce chitosan is achieved by treating the sample with 40-50% aqueous (w/v) NaOH solution
at 90-120°C for 4-5 h. The crude precipitate of chitosan is washed in water and dissolved in
2% aqueous acetic acid. Any insoluble material is removed and the solution is neutralized with
NaOH solution [63].
A hybrid colon-specifi c drug delivery system consisting of the pH-sensitive polymer Eudragit
and chitosan has recently been developed [62]. Chitosan microspheres measuring 2-3 µm in diameter
were prepared by spray-drying a solution of chitosan containing a model drug (sodium diclofenac),
which was subsequently freeze-dried. The microspheres were encapsulated in Eudragit using an
oil-in-oil solvent evaporation method. To do this, the microspheres were dispersed in a solution of
