Microneedle- mediated intrascleral delivery of in situ forming thermoresponsive implants for sustained ocular drug delivery

ObjectivesThis paper describes use of minimally invasive hollow microneedle (HMN) to deliver in situ forming thermoresponsive poloxamer-based implants into the scleral tissue to provide sustained drug delivery. MethodsIn situ forming poloxamer formulations were prepared and investigated for their rheological properties. HMN devices 400, 500 and 600m in height were fabricated from hypodermic needles (i.e. 27, 29 and 30G) and tested for depth of penetration into rabbit sclera. Maximum force and work required to expel different volumes of poloxamer formulations was also investigated. Release of fluorescein sodium (FS) from intrasclerally injected implants was also investigated. Optical coherence tomography (OCT) was used to examine implant localisation and scleral pore-closure. Key findingsPoloxamer formulations showed Newtonian behaviour at 20 degrees C and pseudoplastic (shear-thinning) behaviour at 37 degrees C. Maximum force and work required to expel different volumes of poloxamer formulations with different needles ranged from 0.158 to 2.021N and 0.173 to 6.000N, respectively. OCT showed intrascleral localisation of implants and scleral pore-closure occurred within 2-3h. Sustain release of FS was noticed over 24h and varied with depth of implant delivery. ConclusionsThis study shows that the minimally invasive HMN device can localise in situ forming implants in the scleral tissue and provide sustained drug delivery.