Biodegradable laminar implants for sustained release of recombinant human growth hormone

Due to its short half-life, renal toxicity and necessity for daily subcutaneous injections, recombinant human growth hormone (rhGH) would best be administered in a controlled release formulation. One approach to this is the use of biodegradable laminar implants based on poly(lactic/glycolic) acid. Two PLGA laminar implant formulations (10% w/w), F, and F-2, were designed and statistically compared with a conventional commercial injectable (Norditropin(R)). The following variables were chosen as responses: body weight, organ weights (heart, spleen and thymus), and tibia weights and dimensions. After statistical analysis, the most sensitive responses for detecting differences between formulations were body weight, tibia length and organ weights. Initial in vitro studies of these formulations showed an incomplete gradual release (after 15 days 40% rhGH released from F-1 and 60% from F-2) and in vivo the best results were obtained with F-1. This formulation showed the best growth curve and the highest values of all the above responses. In conclusion, this type of formulation provides a sustained release of rhGH for at least 15 days and a greater efficacy than the frequent administration of the conventional injectable. (C) 2002 Elsevier Science Ltd. All rights reserved.