Importance of in vitro experimental conditions on protein release kinetics, stability and polymer degradation in protein encapsulated poly (d,l-lactic acid-co-glycolic acid) microspheres

Park, Tae Gwan; Lu, Weiqi; Crotts, George

doi:10.1016/0168-3659(94)00084-8

Cited by 235 publications

(121 citation statements)

References 16 publications

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“…4c and Table 1). This result suggests that the initially undissociated NH 4 Ac complex increases PLGA degradation, as extensive chain cleavage resulting in individual amino acids has been associated with the accumulation of PLGA monomers [16,33]. However, the degree of acylation in the NH 4 Ac films was slightly greater than in the control, which is unexpected for more acidic conditions [16].…”

Section: Discussioncontrasting

confidence: 44%

Effect of excipients on PLGA film degradation and the stability of an incorporated peptide

Houchin

Neuenswander

Topp

2007

Journal of Controlled Release

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The effect of pH modifying excipients on the chemical stability of a model peptide (VYPNGA) and the degradation of poly(DL-lactide-co-glycolide)(PLGA) was studied in PLGA films under accelerated storage conditions. pH modifiers included a basic amine (proton sponge), a basic salt (magnesium hydroxide) and two pH buffers (ammonium acetate and magnesium acetate). Changes in film pH were monitored using 13 C NMR, peptide degradation products were quantified by LC/ MS/MS and PLGA degradation was analyzed by TGA, DSC and SEC. Inclusion of pH modifiers had little impact on PLGA degradation. The proton sponge affected an initial decrease in pH but reduced peptide deamidation and chain cleavage relative to an unbuffered control. Magnesium hydroxide produced an initial increase in pH but also showed increased peptide deamidation. Ammonium acetate decreased pH and increased peptide chain cleavage, presumably due to increased PLGA hydrolysis. Magnesium acetate buffer increased the initial pH but resulted in increased peptide loss. The extent of peptide acylation increased in all formulations, most notably in the proton sponge modified films. The effectiveness of pH modifiers in PLGA formulations under storage conditions is dependant on both the mechanism of pH alteration and the peptide degradation reaction of interest.

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Section: Discussioncontrasting

confidence: 44%

Effect of excipients on PLGA film degradation and the stability of an incorporated peptide

Houchin

Neuenswander

Topp

2007

Journal of Controlled Release

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“…The increased water content may result from an increase in polymer hydrophilicity and charge after hydrolysis. An alternate explanation might be pH effects as seen in lactic acid polymers 26,27 . However, in this case, the pH was adjusted frequently to keep the pH nearly constant.…”

Section: Resultsmentioning

confidence: 99%

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

2007

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Novel, bioerodible, thermosensitive poly(NIPAAm-co-dimethyl-γ-butyrolactone), with hydrolysisdependent thermosensitivity, were synthesized by radical polymerization with varying dimethyl-γ-butyrolactone content and the properties of the copolymers were characterized using Differential Scanning Calorimetry (DSC), High Performance Liquid Chromatography (HPLC) in conjunction with Static Light Scattering, Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and acid titration. The lower critical solution temperature (LCST) of the copolymers decreased with increasing dimethyl-γ-butyrolactone content, but then increased after ring-opening hydrolysis of the dimethyl-γ-butyrolactone side group. FTIR and NMR spectra showed the copolymerization of these two monomers and the hydrolysis-dependent ring-opening of the dimethyl-γ-butyrolactone side group. It was also found that there are no low-molecular-weight byproducts but rather dissolution of the polymer chains at 37°C during the time frame of application. Models of the kinetics suggest that the hydrolysis reaction is self-catalytic due to an increase in hydrophilicity, and thus accessible water concentration, caused by ring-opening of the dimethyl-γ-butyrolactone.

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“…This primary emulsion became the discontinuous, or injected, phase for the secondary emulsification. For the second emulsification, 10 ml of the discontinuous phase was injected in the dispersion cell into 150 ml of reverse osmosis water containing 1% PVA and different salt concentrations (40, 33,26,16 g/l). The injection rate was 0.5 ml/min, the stirrer agitation speed was either 600 or 860 rpm and membrane pore diameters of 40 and 20 µm respectively were used.…”

Section: Encapsulated Particle Productionmentioning

confidence: 99%

“…By changing the lactic/glycolic acid ratio of the PLGA molecules it is possible to control the degradation rate. PLGA has been used to prepare tablets to be ingested, scaffolds, nanoparticles for inhalers or intravenous injections and microparticles for subcutaneous depot [4][5][6][7]9,12,[14][15][16][17]. The work reported here produced particles in the range of 40 to 140 µm via membrane emulsification followed by the solvent removal method to produce the PLGA microspheres.…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of PLGA particles for subcutaneous controlled drug release by membrane emulsification

Gasparini

Kosvintsev

Stillwell

et al. 2008

Colloids and Surfaces B: Biointerfaces

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Importance of in vitro experimental conditions on protein release kinetics, stability and polymer degradation in protein encapsulated poly (d,l-lactic acid-co-glycolic acid) microspheres

Cited by 235 publications

References 16 publications

Effect of excipients on PLGA film degradation and the stability of an incorporated peptide

Effect of excipients on PLGA film degradation and the stability of an incorporated peptide

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

Preparation and characterization of PLGA particles for subcutaneous controlled drug release by membrane emulsification

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