Temperature-responsive and biodegradable PVA:PVP k30:poloxamer 407 hydrogel for controlled delivery of human growth hormone (hGH)

Recombinant human growth hormone (rhGH) is used for replacement therapy of pediatric hypopituitary dwarfism. Growth rate in children was observed to be better on the daily injection schedule compared with the currently used therapeutic regimen of thrice a week injection. Thus, a controlled release formulation would overcome the drawback of traditional rhGH therapy such as the need for multiple injections. Poloxamers are a family of triblock copolymers consisting of two hydrophilic blocks of polyoxyethylene separated by a hydrophobic block of polyoxypropylene, which form micelles at low concentrations and form clear thermally reversible gels at high concentrations. We used poloxamer gels to develop a controlled release formulation of hGH. The objective of this study was to develop an in situ gel forming drug delivery system for hGH using the minimum possible ratio of poloxamer 407 (P407). Decreasing the concentration of poloxamer could reduce the risk of hypertriglyceridemia induction. Different additives were added to the poloxamer formulations. It was observed that among different additives polyvinylpyrrolidone k30 (PVP k30) and polyvinyl alcohol (PVA) decrease poloxamer concentration required to form in situ gelation from 18% to 10%. The dynamic viscoelastic properties of the samples were determined. Both the storage modulus and the loss modulus of the samples increased abruptly as the temperature passed a certain point. It can be concluded that combining P407 and PVP and PVA could be a promising strategy for preparation of thermally reversible in situ gel forming delivery systems of hGH with low poloxamer concentration.