title: Microneedle-mediated intrascleral delivery of in situ forming thermoresponsive implants for sustained ocular drug delivery.
abstract: OBJECTIVE
  This 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.
  
  
  METHODS
  In situ forming poloxamer formulations were prepared and investigated for their rheological properties. HMN devices 400, 500 and 600 μm in height were fabricated from hypodermic needles (i.e. 27, 29 and 30 G) 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.
  
  
  RESULTS
  Poloxamer formulations showed Newtonian behaviour at 20°C and pseudoplastic (shear-thinning) behaviour at 37°C. Maximum force and work required to expel different volumes of poloxamer formulations with different needles ranged from 0.158 to 2.021 N and 0.173 to 6.000 N, respectively. OCT showed intrascleral localisation of implants and scleral pore-closure occurred within 2-3 h. Sustain release of FS was noticed over 24 h and varied with depth of implant delivery.
  
  
  CONCLUSIONS
  This study shows that the minimally invasive HMN device can localise in situ forming implants in the scleral tissue and provide sustained drug delivery.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, UK.
authors.forename: Raghu Raj Singh
authors.initials: RR
authors.lastname: Thakur
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fallows
authors.forename: Hannah L
authors.initials: HL
authors.lastname: McMillan
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods*; D019793:Fluorescein / Q000008:administration & dosage; D008845:Microinjections / Q000379:methods*; D009339:Needles; D020442:Poloxamer / Q000008:administration & dosage*; D019736:Prostheses and Implants; D011817:Rabbits; D012212:Rheology; D012590:Sclera / Q000378:metabolism*
chemical_list: D003692:Delayed-Action Preparations; D020442:Poloxamer; D019793:Fluorescein
keywords: microneedle; minimally invasive; optical coherence tomography; poloxamers; sclera