IADR Abstract Archives
Use of nanotechnology to deliver therapeutic agents to modify cranial suture function.
Objectives: Sutures in the craniofacial skeleton are important sites for bone growth. The interest in modulating suture function function has mainly focused on the cranial sutures as part of managing early fusion (Craniosynostosis). Molecular biologists have identified a number of key regulatory proteins that could be the target of novel therapeutic agents to reduce excessive bone formation.
However, the development of new medical agents has now resulted in difficulties in delivering such agents. Local concentrated delivery is desirable to reduce the risk of systemic toxicity and to be clinically significant over a sustained period. The aim of this study was to develop a delivery system that met these objectives of delivering a therapeutic agent Glypican3 to the sutures in a murine model of syndromic Craniosynostosis (Crouzon syndrome).
In conjunction with the department of Chemical engineering a number of different materials have been trialed as use of a delivery system. Titanium was selected as this already widely used in in clinical practice and complications are reported to be rare. However, materials at Nano-level can behave biologically differently so assessment of tissue tolerance was needed.
Methods: Titanium delivery systems were trialed using different shapes and sizes to obtain the ideal characteristics for the particular therapeutic agent. Next, toxicity studies using in vitro using cultured cranial cells were undertaken. Further, the delivery systems were placed in vivo in mice with a “knock-in” mutation in the FGFR2 gene on a Balbc/Swiss background.
Results: Initially, the drug delivery was too fast when tested for drug-release characteristics and biological coatings were added. The final design of the drug delivery titanium Nano-tubules was modified along with the addition of a biological coating to obtain the desired characteristics.
Conclusions: The results confirm that titanium nano-delivery systems are well tolerated by the cells and tissues and have little impact on cranial suture cells in direct contact with them. These initial findings result in further trials using this system in murine models with the loaded with the therapeutic agent Glypican 3 are on-going.
However, the development of new medical agents has now resulted in difficulties in delivering such agents. Local concentrated delivery is desirable to reduce the risk of systemic toxicity and to be clinically significant over a sustained period. The aim of this study was to develop a delivery system that met these objectives of delivering a therapeutic agent Glypican3 to the sutures in a murine model of syndromic Craniosynostosis (Crouzon syndrome).
In conjunction with the department of Chemical engineering a number of different materials have been trialed as use of a delivery system. Titanium was selected as this already widely used in in clinical practice and complications are reported to be rare. However, materials at Nano-level can behave biologically differently so assessment of tissue tolerance was needed.
Methods: Titanium delivery systems were trialed using different shapes and sizes to obtain the ideal characteristics for the particular therapeutic agent. Next, toxicity studies using in vitro using cultured cranial cells were undertaken. Further, the delivery systems were placed in vivo in mice with a “knock-in” mutation in the FGFR2 gene on a Balbc/Swiss background.
Results: Initially, the drug delivery was too fast when tested for drug-release characteristics and biological coatings were added. The final design of the drug delivery titanium Nano-tubules was modified along with the addition of a biological coating to obtain the desired characteristics.
Conclusions: The results confirm that titanium nano-delivery systems are well tolerated by the cells and tissues and have little impact on cranial suture cells in direct contact with them. These initial findings result in further trials using this system in murine models with the loaded with the therapeutic agent Glypican 3 are on-going.