From Bench to Bedside—An Example of an In Situ Hydrogel in In Vivo Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 211

Fig. 1 ReGel phase diagram.
Reproduced from Zentner
et al. [ 4 ]
Regel™ copolymers are biocompatible and biodegradable polymers which exhibit
such reverse thermal gelation properties [ 4 ]. These polymers are triblock copolymers
consisting of A-blocks made up of poly(lactide-co-glycolide) and B-blocks made
up of poly(ethylene glycol) arranged in an ABA or BAB sequence, with a defined
molecular weight and hydrophobic/hydrophilic balance. Modification in the hydro-
phobic/hydrophilic ratio of the polymer constructs, results in Regel™ being water
soluble below room temperature and a gel at body temperature [ 4 ]. As Regel™ is
a physically formed hydrogel, the sol-gel transition occurs within seconds, without
any chemical modification of the constituent co-polymers [ 5 ]. The reversible gela-
tion behavior is presented in the phase diagram (Fig. 1 ), which illustrates the gela-
tion behavior at physiologically relevant temperature (37 °C). This forms the basis
of the biomedical application of Regel™ copolymers as a potential drug carrier. The
polymer is hydrolytically degradable and degrades into lactic acid and glycolic acid
components after a period of time. Another significant aspect to be noted is the water
solubility of the residual polymer which enables its diffusion from the injection site
and subsequent elimination through the kidneys.
Oncogel (ReGel™/Paclitaxel) is a formulation of the chemotherapeutic intratu-
morally injectable drug Paclitaxel, developed by MacroMed Inc. (Salt Lake City,
Utah, USA) for local treatment of solid tumors [ 5 ]. Paclitaxel is an anti-microtu-
bule agent which binds to tubulin-binding sites, causing mitotic arrest and apop-
tosis. Regel™ increases the solubility and stability of hydrophobic drugs such as
paclitaxel, thus using the system (ReGel™/paclitaxel) ensures a sustained drug
release for about 6 weeks. Oncogel is a drug delivery system which combines
controlled release with physical targeting of the tumor site either via intra-lesional
injection or direct placement into the tumor cavity after resection [ 6 - 8 ]. This poses
an advantage over the systemic administration of paclitaxel as it provides con-
tinuous release of the therapeutic agent throughout the tumor irrespective of its
vascular status. It is also established that Oncogel produces minimal on site toxic-
ity, which enhances its possibility of being used as a component of combination