Posted by Cyclodextrins are seldom used in sustained-release formulations, as they are more commonly associated with rapid drug delivery. However, cyclodextrin complexes can be further encapsulated within pharmaceutically acceptable matrices to enable controlled or delayed release.
As an example of such application, a research group from Utrecht, the Netherlands has published their in vivo results [1] on a gel containing bupivacaine, a local anesthetic used in a wide variety of superficial and invasive procedures prepared in the following manner:
Gelatin derivatized with 3-(4-hydroxyphenyl)propionic acid was dissolved in water for injections, mixed with riboflavin, sodium persulfate, and oxidized beta-cyclodextrin (oB-CD). The mixture was then transferred in ring-shaped molds and irradiated with high-intensity visible white light. The resulting hydrogels were washed to remove any remaining reagents. To load bupivacaine, the hydrogels were submerged in a 5 wt% bupivacaine HCl solution followed by incubation in sodium bicarbonate buffer/glycerol (0.1 M, pH 8.5) to induce alkaline crystallization of bupivacaine inside the hydrogels. The bupivacaine loaded hydrogels were then dip coated with PLGA so that the domed surface of the ring-shaped hydrogel was coated, whilst the flat bone-contact surface remained uncoated. Following preparation, the hydrogels were sterilized using gamma irradiation, finally endotoxin content was controlled.
Bupivacaine release from hydrogel rings was sustained for 72 hours in vivo (using a sheep model), closely matching in vitro release profiles, and resulted in high local concentrations at the wound site with minimal systemic exposure. The hydrogel was biodegradable and triggered a typical foreign body response. This formulation shows promise for improving postoperative analgesia and enhancing recovery after spinal surgery.
Some of the authors of the paper are also inventors of the related patent application [2].
References:
[1] Jasper G. Steverink, Floris R. van Tol, Suzanne Bruins, Kwame B. Amponsah, Jessica Marvela, Andre J. Smorenburg, Hein R. Jonkman, Bas J. Oosterman, Marijke R. van Dijk, Jos Malda, Susanna Piluso, Jorrit-Jan Verlaan, Testing a new sustained-release local anesthetic formulation specifically designed for spine surgery in a sheep model, International Journal of Pharmaceutics, Volume 678, 2025, 125731,
https://doi.org/10.1016/j.ijpharm.2025.125731.
[2] WO2020249695 – HYDROGEL FOR IN-VIVO RELEASE OF MEDICATION