The InGell Gamma PCLA-PEG-PCLA tri-block copolymers with aliphatic end groups form micelles in water. The active pharmaceutical ingredients are being mixed-in at lower temperatures and recide either in the micelles or between the micelles depending on the solubility parameters of the compound involved. At lower temperatures, the micelles are dispersed in aqueous solution and they can be homogeneously injected. At body temperature the hydrophobic character of the amphiphilic tri-block copolymers dominates and consequently the micelles rapidly aggregate to form a macroscopic gel. Such in-situ formed macroscopic gels are nicely demonstrated in the picture hereunder. In the corners of the picture "InGell Gamma" gels are visible formed upon injection in rat. The polymer gels have been made radiopaque by covalent modification to make them visible under CT.
The formation of LQP depots is rather similar, but with small differences, which for now we can elude under confidentiality.
Whereas ReGel is based on PEG, lactide and glycolide, InGell Gamma and LQP are based on PEG, caprolactone and usually minor amounts of lactide. The use of caprolactone stabilizes the polymer backbone, allowing longer and better controlled release profiles, with no acid-based degradation in situ.
Gamma and LQP have aliphatic end groups that further tailor the hydrophobicity of the triblock copolymer, affecting the retention properties of the depot. The end-groups effectively reduce burst effects, which is one of the challenges in using in-situ forming depots for drug delivery.
Another unique aspect of InGell Gamma and InGell LQP is the ability to solubilize hydrophobic drug molecules. These drugs are actually drawn into the Gamma-micelles, or they are solubilized amongst the LQP-polymers, greatly enhancing the loading capability of any water-borne formulation. This allows the user to load unprecedented levels of small hydrophobic drugs without creating insoluble crystals in situ... up to 25% of the weight of the injected formula.
More on basic scientific backgrounds about injectable hydrogels can be found in the articles listed below. It should be noted, however, that the articles do not exactly reflect InGell Gamma's features and science moved forward since publication of the articles listed. Articles on LQP have not yet been published, as we have kept the technology under the radar until the patent was published.
Heller, J. Patient-friendly bioerodible drug delivery systems. J Control Release 133, 88-89 (2009).
Jo, S., Kim, J. & Kim, S.W. Reverse thermal gelation of aliphatically modified biodegradable triblock copolymers. Macromol Biosci. 6, 923-928 (2006).
Bae, S.J. et al & Kim, S.W. et al. Thermogelling poly(caprolactone-b-ethylene glycol-b-caprolactone) aqueous solutions. Macromolecules 38, 5260-5265 (2005).
Petit, A. et al., Modulating rheological and degradation properties of temperature-responsive gelling systems composed of blends of PCLA-PEG-PCLA triblock copolymers and their fully hexanoyl capped derivatives, Acta Biomaterialia (2012), doi: http://dx.doi.org/10.1016/j.actbio.2012.07.044