A month–long effect from a single injection of microencapsulated human growth hormone

Johnson, OluFunmi L.; Cleland, Jeffrey L.; Lee, Hye Jung; Charnis, Margarita; Duenas, Eileen; Jaworowicz, Warren; Shepard, Douglas; Shahzamani, Azin; Jones, Andrew J. S.; Putney, Scott D.

doi:10.1038/nm0796-795

Cited by 285 publications

(129 citation statements)

References 29 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…None the less, recent dramatic improvements in vector technology 23 suggest that in the near future, longer lived, non-(or less) immunogenic adenovirus-mediated gene transfer will be feasible. Many other methods have been described in attempts to develop practical means of stable systemic therapeutic protein delivery, including the use of a variety of re-engineered and implanted cells 5,[7][8] for growth hormone. None of these has, as yet, been of practical therapeutic value.…”

Section: Discussionmentioning

confidence: 99%

“…3 While the availability of recombinant human growth hormone (rhGH) has alleviated concerns about the coadministration of noxious contaminants with hGH purified from human cadaveric pituitaries, 4 there still exists dissatisfaction with daily rhGH injections. 3,[5][6][7][8][9] Gene transfer presents an attractive alternative for the delivery of therapeutic proteins to the bloodstream. Ideally, the gene of interest should be administered to a target tissue which is readily accessible and capable of delivering therapeutic levels of active circulating protein.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

Goldsmith

Marmary

et al. 1998

Gene Ther

View full text Add to dashboard Cite

We have previously suggested that although salivary were approximately 16 ng/ml and rat insulin-like growth glands function in an exocrine manner they might none the factor-1 was elevated approximately 25%. Moreover, less offer a useful way to deliver therapeutic proteins sysserum chemistry profiles of rats subjected to in vivo gene temically. As a direct functional test of this hypothesis, we transfer displayed alterations in the BUN:creatinine ratio constructed a recombinant adenovirus (AdCMVhGH) and triglyceride levels presumably reflecting the anabolic encoding human growth hormone (hGH) and then studied actions of the hGH. These results provide the first demonthe biological action of hGH produced following transfer of stration of systemic biological action from a transgene prothe hGH gene to rat submandibular glands. At 48 h followduct secreted in an endocrine fashion from the salivary ing infusion of AdCMVhGH into these glands via canglands. nulation of the main excretory duct, serum levels of hGH

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

Goldsmith

Marmary

et al. 1998

Gene Ther

View full text Add to dashboard Cite

show abstract

“…This matrix has been extensively used in implantable materials and causes little local inflammatory response (Sanders et al, 1986;Johnson et al, 1996;Shive and Anderson, 1997). The release of naltrexone from the PLG matrix, as indicated by plasma naltrexone concentrations, was relatively independent of the route of administration (ie s.c. vs i.m.).…”

Section: Discussionmentioning

confidence: 99%

Vivitrex®, an Injectable, Extended-Release Formulation of Naltrexone, Provides Pharmacokinetic and Pharmacodynamic Evidence of Efficacy for 1 Month in Rats

Bartus

Emerich

Hotz

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

While oral naltrexone is effective in treating alcohol and opiate dependencies, poor patient adherence and widely fluctuating plasma levels limit its efficacy. To overcome these problems, an extended-release formulation of naltrexone (Vivitrex s ) was developed by encapsulating naltrexone into injectable, biodegradable polymer microspheres. Pharmacokinetic studies in rats demonstrated that this formulation produced stable, pharmacologically relevant plasma levels of naltrexone for approximately 1 month following either subcutaneous or intramuscular injections. While rats receiving placebo microspheres demonstrated a pronounced analgesic response to morphine in the hot-plate test, morphine analgesia was completely blocked in rats treated with extended-release naltrexone. This antagonism began on day 1 following administration and lasted for 28 days. Rats reinjected with extended-release naltrexone 34 days after the initial dose and tested for another 35 days showed consistent suppression of morphine analgesia for an additional 28 days. mOpioid receptor density, as measured by [ 3 H]DAMGO autoradiography, increased up to two-fold following a single injection of extended-release naltrexone. Saturation binding assays using [3 H]DAMGO showed changes in the midbrain and striatum at 1 week after extended-release naltrexone administration, and after 1 month in the neocortex. These receptor increases persisted for 2-4 weeks after dissipation of the morphine antagonist actions of naltrexone. These data suggest that therapeutically relevant plasma levels of naltrexone can be maintained using monthly injections of an extended-release microsphere formulation, and that changes in m-opioid receptor density do not impact its efficacy in suppressing morphine-induced analgesia in the rat. Clinical trials of extended release naltrexone for treating alcohol and opiate dependency are currently ongoing.

show abstract

“…Nutropin Depot ® (Genentech, Inc., South San Francisco, California, USA) was developed as a biodegradable microsphere form of rhGH, achieving a 1-month sustained-release. 11 Twice-monthly administration is recommended for children only. Mainly adverse events related to the injection site, included nodules (60% of injections), erythema (54%), and postinjection pain (36%) in 1,483 injections.…”

Section: Microspheres/microparticlesmentioning

confidence: 99%

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Cai¹,

Xu²,

Yuan³

et al. 2014

IJN

View full text Add to dashboard Cite

Since the availability of recombinant human growth hormone (rhGH) enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot ® microsphere and injectors (Zomajet ® , Serojet ® , and NordiFlex ® ). Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product.

show abstract

A month–long effect from a single injection of microencapsulated human growth hormone

Cited by 285 publications

References 29 publications

Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

Vivitrex®, an Injectable, Extended-Release Formulation of Naltrexone, Provides Pharmacokinetic and Pharmacodynamic Evidence of Efficacy for 1 Month in Rats

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Contact Info

Product

Resources

About