Development of a novel sustained release formulation of recombinant human growth hormone using sodium hyaluronate microparticles

Kim, Jong Hun; Hahn, Sei Kwang; Kim, Myung Jin; Kim, Duk Hee; Lee, Young Phil

doi:10.1016/j.jconrel.2005.02.012

Cited by 133 publications

(62 citation statements)

References 22 publications

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“…Both hyaluronic acid and chondroitin sulfate, which are found naturally in the joint cavity, have been used to improve the physical features of spray-dried powders and been found to have the potential to modulate drug release. 37,38 The aim of this study was to encapsulate methylprednisolone into microparticles, to assess the influence of excipients on in vitro drug release under sink conditions, and to provide a preliminary evaluation of the toxicity of this drug delivery system, given the prospect of its eventual application in the clinical treatment of inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Tobar-Grande¹,

Godoy²,

Bustos³

et al. 2013

IJN

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Abstract:In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis.

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Section: Introductionmentioning

confidence: 99%

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Tobar-Grande¹,

Godoy²,

Bustos³

et al. 2013

IJN

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“…Release of hGH from the hyaluronate microspheres was extended to 50 h with 80% of hGH loads released in the first 24 h (94). A high performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis assay of hGH released from the hyaluronate microspheres showed no protein aggregation, and blood serum assay using beagle dogs exhibited an area under the curve featured with Cmax of 69.5±8.0 ng/ml and Tmax between 10 and 12 h. A single injection induced elevation of serum IGF-I level until the 6th day (95). For some delicate proteins, especially those with net positive charges at native states, how the negative charges of hyaluronate affect protein stability was not discussed.…”

Section: Microencapsulation Using Water Soluble Materialsmentioning

confidence: 93%

“…Hahn et al demonstrated oil-coated hyaluronate microspheres for one-injection-per-week administration of hGH (94,95). The microspheres were prepared by spray drying an aqueous cosolution containing sodium hyaluronate, hGH, and lecithin.…”

Section: Microencapsulation Using Water Soluble Materialsmentioning

confidence: 99%

Polymer-Based Sustained-Release Dosage Forms for Protein Drugs, Challenges, and Recent Advances

Jin

2008

AAPS PharmSciTech

112

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Abstract. While the concept of using polymer-based sustained-release delivery systems to maintain therapeutic concentration of protein drugs for extended periods of time has been well accepted for decades, there has not been a single product in this category successfully commercialized to date despite clinical and market demands. To achieve successful systems, technical difficulties ranging from protein denaturing during formulation process and the course of prolonged in vivo release, burst release, and incomplete release, to low encapsulation efficiency and formulation complexity have to be simultaneously resolved. Based on this updated understanding, formulation strategies attempting to address these aspects comprehensively were reported in recent years. This review article (with 134 citations) aims to summarize recent studies addressing the issues above, especially those targeting practical industrial solutions. Formulation strategies representative of three areas, microsphere technology using degradable hydrophobic polymers, microspheres made of water soluble polymers, and hydrophilic in vivo gelling systems will be selected and introduced. To better understand the observations and conclusions from different studies for different systems and proteins, physicochemical basis of the technical challenges and the pros and cons of the corresponding formulation methods will be discussed.

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“…22 LB03002 was an injectable rhGH suspension of microparticles in which rhGH was incorporated into sodium hyaluronate at the optimized ratio of 1:3 (loading efficiency of 25%). rhGH release from microparticles could last for 72 hours and elevate IGF-1 level for 6 days in Beagle dogs.…”

mentioning

confidence: 99%

“…In cases of Nutropin Depot ® , the concentration of PLGA microsphere suspensions is 105.5 mg/mL. 22 To deliver the maximum amount, the loading efficiency should be 17.1% or more. Although we can inject more volume to make up the scarcity of rhGH in low-loading efficiency formulations, adverse events such as nodules may be triggered more frequently as a result.…”

mentioning

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

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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.

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Development of a novel sustained release formulation of recombinant human growth hormone using sodium hyaluronate microparticles

Cited by 133 publications

References 22 publications

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Polymer-Based Sustained-Release Dosage Forms for Protein Drugs, Challenges, and Recent Advances

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

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