Structural Stability of Recombinant Human Growth Hormone (r-hGH) as a Function of Polymer Surface Properties

PURPOSE: Despite the fact that r-hGH was first approved for use by FDA in 1995 and the conventional dosage form in the market has a limitation of daily subcutaneous injections, there remains a lack of sustained delivery system in the market. Nutropin depot, a long-acting dosage form of r-hGH was approved for marketing by FDA in 1999, however, it was discontinued in 2004. Since then, unabating efforts have been made to develop biodegradable polymer based formulations for r-hGH delivery. However, grey area is the comprehension of structural stability of r-hGH at an interface with the polymer and it is of utmost important to attain safe and efficacious sustained delivery system. The purpose of this study was to evaluate the changes in structure of r-hGH upon adsorption at biodegradable PLGA nanoparticles of different hydrophobicity as a function of pH.

METHODS: DLS, fluorescence spectroscopy, and CD were collectively employed to evaluate structural changes in r-hGH.

RESULTS: The studies revealed that r-hGH is most stable with low to high hydrophobicity PLGA grades under pH 7.2 followed by 5.3.

CONCLUSION: Overall, the nature and magnitude of structural changes observed has a strong dependence on the pH and differences and degree of hydrophobicity of PLGA.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:35

Enthalten in:

Pharmaceutical research - 35(2018), 5 vom: 15. März, Seite 98

Sprache:

Englisch

Beteiligte Personen:

Shah, Vaishnavi Rohitkumar [VerfasserIn]
Gupta, Pardeep K [VerfasserIn]

Links:

Volltext

Themen:

12629-01-5
1SIA8062RS
Circular dichroism spectroscopy (CD)
Dynamic light scattering (DLS)
Fluorescence spectroscopy
Human Growth Hormone
Journal Article
Nanoparticles
Poly (lactide-co-glycolide) (PLGA)
Polylactic Acid-Polyglycolic Acid Copolymer
Recombinant Proteins
Recombinant human growth hormone (rhGH)
Secondary structure
Tertiary structure

Anmerkungen:

Date Completed 06.06.2019

Date Revised 06.06.2019

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s11095-018-2372-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM28202459X