Enhanced loading and activity retention of bioactive proteins in hydrogel delivery systems

Gehrke, Stevin H.; Uhden, Lorelle H.; McBride, James F.

doi:10.1016/s0168-3659(98)00019-4

Cited by 87 publications

(64 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A second method consists in immersing and soaking the polymeric particles/articles, previously synthesized, into a solution, or dispersion, containing the drugs to impregnate/infuse. Usually an aqueous solution, or dispersion, is used but organic solutions or dispersions can also be employed, depending essentially on drug and polymer solubility or on other considerations like, for example, solvent toxicity and solvent facility to be removed/evaporated [34][35][36][37][38][39]. However, these methods present several disadvantages, like the use of sometimes toxic organic solvents, which have to be removed by heating, undesired drug reactions, drug and polymer photochemical and thermal degradation, low incorporation yields and heterogeneous drug dispersion.…”

Section: Introductionmentioning

confidence: 99%

Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives

Braga

Pato

Silva

et al. 2008

The Journal of Supercritical Fluids

107

View full text Add to dashboard Cite

In this work, three chitosan derivatives (N-carboxymethyl chitosan (CMC), N-carboxybutyl chitosan (CBC) and N-succinyl chitosan (SCC)) were impregnated with flurbiprofen (an anti-inflammatory drug) and timolol maleate (an anti-glaucoma drug), using a supercritical solvent impregnation (SSI) technique (and employing high pressure CO 2 and CO 2 + EtOH mixtures) in order to develop hydrogel-type ophthalmic drug delivery applications. Impregnation experiments were carried out from 9.0 up to 14.0 MPa, and at 303.0, 313.0 and 323.0 K. The resulting polymeric drug delivery systems, as well as other polymeric samples processed in CO 2 , were characterized by FTIR spectroscopy and scanning electron microscopy (SEM). Drug release kinetics studies were performed for all prepared systems. The effects of impregnation pressure and temperature on the release kinetics results were studied and compared to the traditional soaking impregnation method. For the same operational conditions, results confirmed that the three different (chemically and physically) polymeric structures conditioned the impregnation and the drug release processes. Despite the final released drug mass is always the result of the employed operational impregnation conditions and of the very complex relative specific interactions that may occur between all species present in the system (drugs, polymers, CO 2 and ethanol), results showed that, for N-carboxymethyl chitosan, the predominant effects in the impregnation process seemed to be the solubility of drugs in CO 2 and in CO 2 + EtOH mixtures, as well as the swelling and plasticizing effect of CO 2 and ethanol on the polymer. Finally, the SSI method proved to be a more efficient and "tunable" impregnation process than the traditional impregnation of drugs by a soaking method. Therefore, and using this "tunable" SSI method, these N-chitosan derivatives-based ophthalmic drug delivery systems can be easily and efficiently prepared taking in consideration the desired drug levels according to patients needs.

show abstract

Section: Introductionmentioning

confidence: 99%

Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives

Braga

Pato

Silva

et al. 2008

The Journal of Supercritical Fluids

107

View full text Add to dashboard Cite

show abstract

“…The inclusion of PEG in the formulation improved insulin loading capacity, possibly by masking surface negative charges in the CAP particles due to the presence of PO 4 ions. 9 Other reports also indicate enhanced protein absorption for polymeric microparticles 10 and hydrogels 11 in the presence of PEG.…”

Section: Introductionmentioning

confidence: 94%

Evaluation of novel particles as pulmonary delivery systems for insulin in rats

García-Contreras

Morçöl²,

Bell³

et al. 2003

AAPS PharmSci

View full text Add to dashboard Cite

KEYWORDS:pulmonary delivery, insulin, CAP-PEG particles, pharmacokinetics, pharmacodynamicsThe purpose of the study was to evaluate the influence of calcium phosphate (CAP) and polyethylene glycol (PEG) particles on the systemic delivery of insulin administered by the pulmonary route. Two methods of pulmonary delivery were employed: intratracheal instillation and spray instillation. Insulin-CAP-PEG particles in suspension (1.2 U/kg, 110-140 μL) were administered to the lungs of fasted rats by intratracheal instillation (INCAPEG) or spray instillation (SINCAPEG). Control treatments consisted of insulin solution (1.2 U/kg) by intratracheal instillation, spray instillation, and subcutaneous administration (SC). Plasma concentrations of insulin and glucose were determined by chemiluminescence and colorimetric methods, respectively. Data were analyzed by compartmental and non-compartmental methods, and pharmacokinetic (PK) and pharmacodynamic (PD) parameters of insulin disposition were determined. PK analysis suggested that insulin administered in particles had a longer half-life, a longer mean residence time, and a smaller rate of elimination than insulin in solution. In addition, insulin bioavailability after SINCAPEG was 1.8-fold that of insulin solution administered SC. PD analysis showed that smaller areas under the effect curve and, conversely, larger areas above the effect curve were obtained after INCAPEG in comparison to insulin solution. The magnitude of this effect was increased after SINCAPEG. The presence of CAP-PEG particles appears to positively influence the disposition of insulin administered to the lungs of Sprague-Dawley rats. Spray instillation appears to be a more efficient method of delivering insulin to the lungs of rats than intratracheal instillation.

show abstract

“…Even glasses exchange protons (surface pKa) and may release some ions in water [45,46]. The reorganization of polymers explains the large amounts of protein that can be adsorbed on certain hydrogels [47] or multilayered polyelectrolyte films [48]. It would therefore be important to also consider the reorganization of the material surface during protein adsorption, especially for "soft" surfaces.…”

Section: 3mentioning

confidence: 99%

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

Ballet¹,

Boulangé²,

Bréchet³

et al. 2010

Bulletin of the Polish Academy of Sciences: Technical Sciences

View full text Add to dashboard Cite

Abstract. Protein adsorption on solid surfaces is a widespread phenomenon of large biological and biotechnological significance. Conformational changes are likely to accompany protein adsorption, but are difficult to evidence directly. Nevertheless they have important consequences, since the partial unfolding of protein domains can expose hitherto hidden amino acids. This remodeling of the protein surface can trigger the activation of molecular complexes such as the blood coagulation cascade or the innate immune complement system. In the case of extracellular matrix, it can also change the way cells interact with the material surfaces and result in modified cell behavior. In this review, we present direct and indirect evidences that support the view that some proteins change their conformation upon adsorption. We also show that both physical and chemical methods are needed to study the extent and kinetics of protein conformational changes. In particular, AFM techniques and cryo-electron microscopy provide useful and complementary information. We then review the chemical and topological features of both proteins and material surfaces in relation with protein adsorption. Mutating key amino acids in proteins changes their stability and this is related to material-induced conformational changes, as shown for instance with insulin. In addition, combinatorial methods should provide valuable information about peptide or antibody adsorption on well-defined material surfaces. These techniques could be combined with molecular modeling methods to decipher the rules governing conformational changes associated with protein adsorption.

show abstract

Enhanced loading and activity retention of bioactive proteins in hydrogel delivery systems

Cited by 87 publications

References 26 publications

Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives

Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives

Evaluation of novel particles as pulmonary delivery systems for insulin in rats

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

Contact Info

Product

Resources

About