Sustained Release of Recombinant Human Growth Hormone from Bioresorbable Poly(ester urea) Nanofibers

Abstract

Recombinant human growth hormone (rhGH) has been used clinically for several decades. However, rhGH has a short half-life in vivo and therefore for efficacy requires frequent subcutaneous injection, leading to pain and poor patient compliance. An effective rhGH delivery system able to continuously release rhGH over a comparatively long period (generally over a month) would be a significant clinical advance. In this study, a novel long-duration release strategy of rhGH was developed by encapsulating sugar glass-stabilized rhGH in electrospun, bioresorbable poly­(ester urea) (PEU) nanofibers. The rhGH was found to be randomly dispersed among the fibers, and sustained rhGH release with only a modest burst was observed for at least 6 weeks as studied by a bicinchoninic acid (BCA) protein assay. Significantly, the released rhGH remained bioavailable and bioactive as determined by an Nb2 cell bioassay specific for rhGH. Our results suggest the feasibility of this system as an effective long-term sustained release strategy for rhGH and potentially other therapeutic proteins.

Sustained micellar delivery via inducible transitions in nanostructure morphology

“…Targeted nanocarrier delivery systems are primarily administered by bolus intermittent injections and infusions, with few options available for sustained delivery 7 . Sustained delivery platforms have proven highly advantageous for drug administration, particularly for long-term processes such as wound healing 8 , 9 , hormone therapy 10 , 11 , and transplant tolerance 12 , 13 , and incorporation of nanocarriers may further improve the efficacy and flexibility of these applications 14 , 15 . Due to the physicochemical similarities and cellular biodistributions between nanoscale materials and viruses, nanocarriers have demonstrated considerable advantages for the targeting and modulation of phagocytic antigen-presenting cells (APCs) that are critical for eliciting immune responses during vaccination and immunotherapy 1 , 2 , 16 , 17 .…”

Protein encapsulation by electrospinning and electrospraying

“…A sustained GH release system was created by stabilisation of the hormone within sugar glass nanoparticles, which were subsequently encapsulated in PCL or poly(ester urea) electrospun fibres. GH release was observed for a period of 6 weeks with minimal burst, and the released protein maintained its bioactivity in in vitro cellular assays [175].…”

Design and applications of protein delivery systems in nanomedicine and tissue engineering

“…Meng et al reported the synthesis of Pluronic F127 (PF127)/D-α-tocopheryl polyethylene glycol succinate (TPGS) micelle by thin-film hydration to specifically deliver proteins to the brain [23]. In another study, Gao et al reported the stabilization of recombinant human growth hormone (rhGH) by sugar glass NPs obtained from inverse micelles [24].…”

“…As for the Bradford assay, the detection limits can vary from a kit to another but are usually ranging from 0.5 to 20 µg.mL -1 , with a possible modification when using microplates to perform the test. This technique has also been used for a wide variety of proteins: BSA [97,124], lysozyme [46,124], OVA, IgG [124], rhGH [24], human chitin binding domain-modified beta-lactamase (ChBD-BlaP)…”

“…A protein delivery system has also been proposed for the treatment of short stature children, and more precisely for the delivery of rhGH [24]. Indeed, this disease can be caused by a deficiency in growth hormone and this one is known to promote longitudinal bone growth.…”