Elastic polymeric capsules for osmosis-driven vaccine delivery

The development of vaccines represents one of the most impactful milestones in the improvement of global health over the last 200 years1. After the first administration of an antigen, the delivery of a booster is usually required to potentiate the immunostimulatory properties of the antigen2. Despite the undeniable success of vaccines, delivery could be improved. The use of controlled-release technology could circumvent the need for multiple interventions for administering booster doses. In this project, osmotic pressure is exploited as a trigger for the spontaneous release of the booster from a subcutaneous polymeric capsule after a given lag time.

Methodology:
Implantable capsules made of crosslinked poly(ɛ-caprolactone) (xPCL), non-crosslinked PCL, and a crosslinked copolymer of ɛ-caprolactone and lactide were prepared by dip coating. Glucose was used as the osmotic agent and the food dye Brilliant blue FCF was employed to assess the osmosis-driven release kinetics. The devices were loaded with 70 µL of the glucose/dye stock solution, capped and incubated in PBS at 37 °C for up to 72 days in order to assess water uptake, and dye release through UV spectrophotometry. The cytotoxicity of the devices was evaluated by performing WST-1 and Alamar blue assays using macrophages and fibroblasts.
Results: All capsules showed a gradual water uptake over several weeks, followed by a rupture which initiated a partial instant release followed by a trickle. The devices made of xPCL released a higher amount of payload at burst (10 %) than those made of PCL, which released only 1% of their total load. These results confirmed that a higher elastic recovery is required in order to increase the release at burst. The capsules made with the copolymer released the highest amount of payload at burst (62% of the total). This was due to the crosslinked and amorphous nature of the copolymer, which endows it with a higher elastic recovery in comparison with that of the semi-crystalline materials (PCL and xPCL). With regard to the toxicity of the materials, the results obtained in vitro showed that the viability of the cells grown on the polymers was comparable to that of cells grown on tissue culture polystyrene. Therefore, these materials did not cause cytotoxic responses on the cells used in the experiments performed.
Conclusions: The results showed herein demonstrated the delayed burst release of a dye encapsulated in devices manufactured with a resorbable, non-cytotoxic polymer. The devices made of poly(ɛ-caprolactone-co-lactide) released approximately 6 to 60 times more payload at burst than the capsules made of xPCL or PCL respectively. The cytotoxicity studies performed in vitro showed that the materials used for the synthesis of the capsules did not cause toxic responses in the cells used for testing.
References
1. Wallis, J. et al., Clin. Exp. Immunol. 2, 189-204 (2019).
2. Saroja et al., Int. J. Pharm. Investig. 2, 64-74 (2011).