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76 Smart Nanomaterials for Sensor Application Singh and Chen
In 1983 the first usable implant, Norplant ® , which releases the drug, levonorgestrel, through six capsules,
was approved by the Finnish national drug regulatory authority. Since then, several more implants have
been approved and others are under development (Table 1). The contraceptive implants have been approved
in more than 60 countries and used by ~11 million women worldwide.
THERMOSENSITIVE POLYMERS
Aqueous solutions of some polymers undergo sol-to-gel transition in response to temperature changes. The
drugs can be mixed in a sol state and injected using a syringe into subcutaneous layers to form a depot
system. The reverse thermo-responsive phenomenon is usually known as Reverse Thermal Gelation (RTG)
and it constitutes one of the most promising strategies for the development of injectable systems for
biomedical applications. Water solutions of these polymers display low viscosity at ambient temperature,
and exhibit a sharp viscosity increase following a small temperature rise, producing a semi-solid gel at body
temperature. There are numerous RTG displaying polymers such as Poly (N-isopropylacrylamide)
(PNIPAAM), Poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblocks (PEO-PPO-
PEO), ethyl (hydroxyethyl) cellulose (EHEC) and poly (ethylene glycol)-poly (lactic acid)-poly (ethylene
glycol) triblocks (PEG-PLA-PEG). Aqueous solutions of these polymers have a Lower Critical Solution
Temperature (LCST), resulting in the viscosity increase, upon heating above this temperature [15].
Numerous polymers show abrupt changes in solubility as a function of environmental temperature. The poly-
NIPAAM exhibits a rather sharp LCST of ~32°C. However, poly-NIPAAM exhibits toxicity therefore it is not
suitable for biomedical applications. It activates platelets on contact with blood along with non-degradability,
makes it difficult to get FDA approval. Therefore a vast majority of the drug delivery system which employs
LCST, use block copolymers of PEO and PPO because of FDA approval. Triblock PEO-PPO-PEO copolymers
(Pluronics or Poloxamers) are available in a variety of compositions and are of particular interest, as their
gelation phenomena have been well studied. They have shown gelation at body temperature at a concentration
over 15% w/w. However, these concentrations of a surfactant lead to notable cytotoxicity. Furthermore,
elevated levels of plasma cholesterol and triglycerides resulting from the chronic administration of poloxamer
containing drug formulations to patients may potentially hinder therapeutic outcome.
Block copolymers consisting of a hydrophobic polyester segment and a hydrophilic PEG segment have
attracted large attention due to their biodegradability, biocompatibility, and tailor-made properties. Various
kinds of block copolymers have been developed to date and can be classified according to their block
structure as AB diblock, ABA or BAB triblock, multi-block, branched block, star-shaped block, and graft
block copolymers (Fig. 1), in which A is a hydrophobic block made up of biodegradable polyesters (PLA,
PGA, or PLGA) and B is a hydrophilic PEG block. A wide variety of drug formulations, such as
micro/nano-particles, micelles, hydrogels, and injectable drug delivery systems have been developed using
PLGA-PEG block copolymers [16-19].
The use of block copolymers in drug delivery was first proposed in the early 1980s. The graft copolymers
of PEG–g–PLGA and PLGA–g–PEG with sol-to-gel transitions at ~30°Cwere developed [20-21]. PEG–g–
PLGA copolymers have hydrophilic backbones and form gels with short durability, whereas PLGA–g–PEG
copolymers have hydrophobic backbones and form much more durable gels. By mixing the two
copolymers, the durability of a gel can be controlled from one week to three months. Water-soluble PLA-
PEG copolymers with a relatively low molecule weight PLA block have been found to self-disperse in
water to form polymeric micelles and can be used to solubilize hydrophobic drugs (Riley et al., 2001) [22].
RTG of biodegradable triblock copolymers has been reported. These polymers were triblock copolymers
consisting of A-blocks and B-blocks arranged as BAB or ABA, where A is PLGA or PLA and B is PEG or
PEO. The polymers are soluble in water, forming a free-flowing solution that spontaneously gels at body
temperature to create a water-insoluble gel. The copolymerization of PEG and lactide or lactide/glycolide is
now regarded as a suitable method to achieve new polymeric materials with novel physical, chemical, and
biological properties adaptable to specific uses [23]. The control of drug release can be achieved by the
adjustment of the triblock copolymer compositions [24,25]. These biodegradable, thermally reversible drug