Sustained Delivery of Lactoferrin Using Poloxamer Gels for Local Bone Regeneration in a Rat Calvarial Defect Model.

Young Eun Park,David Shaun Musson,Maureen Watson,Hani Abdeltawab,Mark Zhu,Donna Tuari,Darren Svirskis,Manisha Sharma,Jillian Cornish,Kaushik Chandramouli,Karen E Callon

doi:10.3390/ma15010212

Young Eun Park, David Shaun Musson + Show 9 more

Open Access

https://doi.org/10.3390/ma15010212

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Abstract

Lactoferrin (LF) is a multifunctional milk glycoprotein that promotes bone regeneration. Local delivery of LF at the bone defect site is a promising approach for enhancement of bone regeneration, but efficient systems for sustained local delivery are still largely missing. The aim of this study was to investigate the potential of the poloxamers for sustained delivery of LF to enhance local bone regeneration. The developed LF/poloxamer formulations were liquid at room temperature (20 °C) transforming to a sustained releasing gel depot at body temperature (37 °C). In vitro release studies demonstrated an initial burst release (~50%), followed by slower release of LF for up to 72 h. Poloxamer, with and without LF, increased osteoblast viability at 72 h (p < 0.05) compared to control, and the immune response from THP-1 cells was mild when compared to the suture material. In rat calvarial defects, the LF/poloxamer group had lower bone volume than the controls (p = 0.0435). No difference was observed in tissue mineral density and lower bone defect coverage scores (p = 0.0267) at 12 weeks after surgery. In conclusion, LF/poloxamer formulations support cell viability and do not induce an unfavourable immune response; however, LF delivery via the current formulation of LF200/poloxamer gel did not demonstrate enhanced bone regeneration and was not compatible with the rat calvarial defect model.

Highlights

Lactoferrin (LF) is a glycoprotein that is present in milk and exocrine secretions in mammals
At four weeks after surgery, there was no difference in the mean bone volume (BV) and tissue mineral density (TMD) between the control and LF200/poloxamer groups (Figure 5)
At 12 weeks, the group treated with the LF200/poloxamer had lower mean BV (p = 0.0435) than the control group, but the TMD was similar in the two groups (Figure 5)

Summary

Introduction

Lactoferrin (LF) is a glycoprotein that is present in milk and exocrine secretions in mammals. It has antimicrobial and immunomodulatory properties and can increase bone growth [1]. It is susceptible to rapid enzymatic degradation in the body with a very high clearance [10,11,12]. Under such circumstances, it is more desirable to deliver LF locally, preferably by developing a drug delivery system that can provide controlled release of LF for a longer time period at the site of administration. LF is known to have a short half-life; approximately 12 min in rat plasma [13], and a study in rats demonstrated that the subcutaneous administration of LF in solution form provided LF release for up to 5 days, whereas subcutaneous implantation of LF in a hydrogel system provided LF release for up to 14 days [4]

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