Biomedical Engineering Reference
In-Depth Information
6.3.3 P
OLYMERIC
N
ANOPARTICLES
In the past few decades, there has been intensive research in the development of nanoparticles of
biocompatible polymers as an effective drug delivery system for chemotherapy and gene delivery.
The drug is either confi ned to a cavity surrounded by a polymer membrane (nanocapsules) or
uniformly dispersed in a matrix (nanospheres) [14,37-39]. Solid, biodegradable nanoparticles have
various advantages over liposomes. First, by varying the polymer composition and morphology of
the particle, controlled release characteristics can be effectively tuned allowing moderate, constant
doses over prolonged periods of time [14].
The early nanoparticles and microparticles were mainly formulated from poly (alkylcyanoac-
rylate) [36]. Nanoparticles can be prepared by monomer polymerization. Polymeric nanoparticles
approximately 200 nm in diameter have been fabricated by mechanically polymerizing dispersed
methyl or ethyl cyanoacrylate in an aqueous acidic medium with a surfactant [28].
An increasing requirement for the modulated drug delivery of both conventionally and
biotechnology-generated drugs of a high molecular weight and short half-life has received con-
siderable attention in the development of biodegradable polymers and their formulation as a drug
delivery system. The use of biodegradable polymers confers the inherent advantage of alleviating
the need for surgical removal of the delivery system a later date [49].
Biodegradable polymers used in drug delivery research may be broadly classifi ed as natural or
synthetic polymers. The majority of investigations into the use of natural polymers as drug delivery
systems has concentrated on the use of proteins (e.g., collagen, gelatin, and albumin) and polysac-
charides (e.g., starch, dextran, insulin, cellulose, and hyaluronic acid).
Various synthetic degradable polymers have been investigated for the formulation of controlled
drug delivery systems, since they can be synthesized with specifi c properties to suit particular appli-
cations. The most widely investigated biodegradable synthetic polymers are linear aliphatic poly-
esters based on poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic acid-
co
-glycolide)
(PLGA), and poly(
ε
-caprolactone) (PCL). They exhibit important advantages of biocompatibility,
predictability of biodegradation kinetics, ease of fabrication, and regulatory approval. Polyanhydride
polymers and copolymers have attracted considerable interest for the fabrication of drug delivery
system because of their labile anhydride linkages in the polymer structure. In addition, poly(ortho
ester)s and polyphosphazenes have received attention for the formulation of nanoparticulate drug
delivery system [49,50]. Poly(ortho ester)s have the advantage of undergoing control degradation of
some polymeric materials. The degradation of polyphosphazenes and the linkage of reactive drug
molecules to the polymer backbone are also controlled by side-group modifi cation [49,50].
The solubility of a hydrophobic drug may be vastly improved by amphiphilic, block copolymer
micelles. The micellization of block copolymers in a selective solvent of one of the blocks is a
common characteristic of their colloidal properties. When a block copolymer is dissolved in a
liquid that is a thermodynamically good solvent for one block and a precipitant for the other, the
copolymer chains may reversibly associate to form micellar aggregates with properties resembling
those obtained from classical, low molecular weight surfactants. The micelles generally consist
of a swollen core of insoluble blocks surrounded by a fl exible fringe of soluble blocks. Block
copolymeric micelles are typically spherical, nanosized (10-100 nm), supramolecular assemblies
of amphiphilic copolymers as shown in Figure 6.1 [40]. The core of these micelles is a loading
space that accommodates hydrophobic drugs, and the hydrophilic outer shell facilitates dispersal
of micelles in water [26,29,30].
The lower the critical micelle concentration (CMC) value of a given amphiphilic polymer, the
more stable the micelles are even at low net concentration of amphiphile in the medium. This is
important from the practical point of view, since upon dilution with a large volume of blood, micelles
with a high CMC value may dissociate into unimers, and their content may precipitate in the blood
[38]. The core compartment of the pharmaceutical polymeric micelle should demonstrate a high
loading capacity, a controlled release profi le for the incorporated drug, and good compatibility
