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

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Abstract

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.

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Abbreviations

% w/v :

Percentage weight by volume

BSA:

Bovine serum albumin

CD:

Circular dichroism

Dh:

Hydrodynamic diameter

DLS:

Dynamic light scattering

g/cm3 :

Gram per cubic centimeter

kDa:

Kilodalton

MES:

2-(N-morpholine)-ethane sulphonic acid

mg:

Milligram

min:

Minute

ml:

Milliliter

MW:

Molecular weight

MWCO:

Molecular weight cut off

nm:

Nanometer

PDI:

Polydispersity index

pI:

Isoelectric point

PLGA 5050 1A:

Poly (lactic-co-glycolic) acid uncapped polymer, ~ 10 kDa

PLGA 5050 5E:

Poly (lactic-co-glycolic) acid ester endcapped polymer, ~ 50 kDa

PLGA 8515 3 CE:

Poly (lactic-co-glycolic) acid ester endcapped polymer, ~30 kDa

PS:

Polystyrene

r-hGH:

Recombinant human growth hormone

SD:

Standard Deviation

Trp:

Tryptophan

Tyr:

Tyrosine

UV:

Ultraviolet

V:

Volume

г:

Surface Coverage

гPL:

Plateau Surface Coverage

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Authors and Affiliations

  1. University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA

    Vaishnavi Rohitkumar Shah & Pardeep K. Gupta

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  1. Vaishnavi Rohitkumar Shah
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Correspondence to Vaishnavi Rohitkumar Shah.

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Shah, V.R., Gupta, P.K. Structural Stability of Recombinant Human Growth Hormone (r-hGH) as a Function of Polymer Surface Properties. Pharm Res 35, 98 (2018). https://doi.org/10.1007/s11095-018-2372-y

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