Biomedical Engineering Reference
In-Depth Information
charged polylysine was adsorbed onto HA patterns, which led to cell type B adhesion onto space
not covered by cell type A. Coculture of two different cell lines may provide a novel method for
studying cell-cell interactions and tissue engineering.
10.3
POLYELECTROLYTE ENCAPSULATION FOR DRUG/GENE DELIVERY
10.3.1 I
NTRODUCTION
Advanced drug delivery systems are preferred for less administration frequency, fewer side effects,
higher drug concentrations at pathological sites, and longer drug bioavailability [103]. A general
method to achieve better delivery is through encapsulation of drug inside carriers that are made of
biocompatible and biodegradable materials. Polymer microspheres, liposomes, polymer micelles,
polymer-drug conjugate, and polymer implants are commonly used drug delivery systems, either
under clinical trials or in the market. They have shown promising results in treating cancers and
immunological and other diseases that traditional formulations usually fail to match. Still, much
improvement is required in drug carrier design and formulation development. A major disadvantage
is that chlorinated organic solvents are usually involved in fabrication, and this may lead to organic
residues in the system and damage encapsulated materials such as proteins. In addition, incomplete
and poorly controlled release is another major limiting factor that affects therapeutic effi cacy.
LbL self-assembled polyelectrolyte shells, recognized as one of the nanotechnologies that
advanced the fi eld of drug delivery [104], may serve as one of the alternatives to solve the above-
mentioned problems. Polyelectrolyte shells present unique advantages such as (1) easy fabrication
process; (2) no necessity of chlorinated organic solvent; (3) fi ne control of permeability through
membrane thickness and shell wall pore size. The thickness of the capsule wall can be precisely
tuned in the range of a few nanometers by choosing coating materials and number of layers. The
pore size on shell wall membrane can be controlled through different polyelectrolyte pairs and
assembly conditions; (4) broad selection of shell materials. Not only charged polymers, but also
lipids, proteins, and magnetic nanoparticles can be used during shell assembly; (5) shells can be
switched between “open” and “closed” states for triggered release. The loading and the release of
materials could be controlled by tuning environmental conditions such as pH or magnetic fi eld.
There are two major methods for the encapsulation of therapeutic agents inside polyelectrolyte
shells: (1) direct coating of oppositely charged polyelectrolytes onto drug micro/nanoparticles and
(2) loading of drug molecules into hollow polyelectrolyte capsules.
Lyophilization is often used to stabilize various pharmaceutical products, including liposomes,
virus vaccines, protein, and peptide formulations. Lyophilization of polyelectrolyte-encapsulated
drugs are important [105-107]: fi rst, to assure an adequate shelf-life as the majority of physico-
chemical reactions, leading to product instability acceleration when stored in aqueous media,
and second, to achieve sterility of the dosage form by a suitable terminal sterilization technique
(e.g., Gamma radiation). In one recent study, no difference in morphology of polyelectrolyte cap-
sule was observed by SEM examination for the samples resuspended after lyophilization treatment
[108]. This satisfi es that freeze-dried samples should be restored to their original properties, thus
providing opportunities to develop novel pharmaceutical formulations based on LbL self-assembly
technique.
10.3.2 L
OADING
B
IOMACROMOLECULES
INTO
H
OLLOW
P
OLYELECTROLYTE
S
HELLS
Currently, there are about 500 biopharmaceuticals that are either approved or in advanced clinical
trials [109]. Protein drugs are a major branch and can be divided into monoclonal antibodies,
cytokines, hormones, growth factors, and enzymes [110]. More choices are available nowadays
than ever because of the fast advance in biotechnology. In comparison, the formulation tech-
nology is developing in a relatively slow pace, and the gap between high-therapeutic effi ciency
