Investigation of a new injectable thermosensitive hydrogel loading solid lipid nanoparticles

For improving the effectiveness of cancer chemotherapy and avoiding rapid clearance of solid lipid nonoparticles (SLN) from the systemic circulation following systemic administration, 2-methoxyestradiol (2-ME) as model drug, PLGA-PEG-PLGA as hydrogel material, an injectable SLN loaded hydrogel was developed. Integrity of SLN within and released from the hydrogel was confirmed by direct visualization by a scanning electron microscope (SEM), particle size measurement by laser light scattering, and free drug concentration in the release medium by ultracentrifugation. Moreover, in vitro release, thermo-sensitive properties and rheological behavior were investigated. The results indicated that SLN were stable in the hydrogel. In the release medium, most 2-ME existed in the SLN and intact 2-ME SLN could be released from the hydrogel for a prolonged period over 46 days. Their concentration showed a significant effect on the release rate, in contrast to particle size and pH value of the release medium. In addition, the SLN loaded hydrogel could still exhibit reversible thermo-sensitive properties and better syringeability. These results suggested that the SLN loaded hydrogel could transport SLN to the target site and control prolonged release of SLN, which may increase the efficacy of cancer chemotherapy.