Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “stability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources
PubMed1998

Contribution of a conserved asparagine to the conformational stability of ribonucleases Sa, Ba, and T1.

The contribution of hydrogen bonding by peptide groups to the conformational stability of globular proteins was studied. One of the conserved residues in the microbial ribonuclease (RNase) family is an asparagine at position 39 in RNase Sa, 44 in RNase T1, and 58 in RNase Ba (barnase). The amide group of this asparagine is buried and forms two similar intramolecular hydrogen bonds with a neighboring peptide group to anchor a loop on the surface of all three proteins. Thus, it is a good model for the hydrogen bonding of peptide groups. When the conserved asparagine is replaced with alanine, the decrease in the stability of the mutant proteins is 2.2 (Sa), 1.8 (T1), and 2.7 (Ba) kcal/mol. When the conserved asparagine is replaced by aspartate, the stability of the mutant proteins decreases by 1.5 and 1.8 kcal/mol for RNases Sa and T1, respectively, but increases by 0.5 kcal/mol for RNase Ba. When the conserved asparagine was replaced by serine, the stability of the mutant proteins was decreased by 2.3 and 1.7 kcal/mol for RNases Sa and T1, respectively. The structure of the Asn 39 --> Ser mutant of RNase Sa was determined at 1.7 A resolution. There is a significant conformational change near the site of the mutation: (1) the side chain of Ser 39 is oriented differently than that of Asn 39 and forms hydrogen bonds with two conserved water molecules; (2) the peptide bond of Ser 42 changes conformation in the mutant so that the side chain forms three new intramolecular hydrogen bonds with the backbone to replace three hydrogen bonds to water molecules present in the wild-type structure; and (3) the loss of the anchoring hydrogen bonds makes the surface loop more flexible in the mutant than it is in wild-type RNase Sa. The results show that burial and hydrogen bonding of the conserved asparagine make a large contribution to microbial RNase stability and emphasize the importance of structural information in interpreting stability studies of mutant proteins.

Asparagine↗
PubMed1998

Mutagenesis of a buried polar interaction in an SH3 domain: sequence conservation provides the best prediction of stability effects.

The SH3 domain from the Fyn tyrosine kinase possesses a buried hydrogen bond between the side chains of a glutamate (Glu24) and a serine (Ser41) residue. Multiple amino acid substitutions were made at these positions to determine the role of this interaction in the stability and conformational specificity of the domain and to assess the relationship between the thermodynamic stability of mutants and sequence conservation seen in the SH3 domain family. Analysis of single and double alanine mutations indicated that the Glu24-Ser41 interaction contributes 0.50 kcal/mol to the stability of the domain. However, disruption of the Glu24-Ser41 interaction did not impair peptide binding function, suggesting that the interaction is not critical for conformational specificity. The stability of the domain was not increased by the replacement of these residues with different combinations of hydrophobic residues or with potential salt bridge forming residues. Despite their similar structural roles in the Fyn SH3 domain, the Ser41 position was considerably more tolerant to substitution than was the Glu24 position. An alignment of >350 different SH3 domains has been completed in our laboratory. A statistically significant correlation was found between the conservation data for the Glu24 and Ser41 positions and the thermodynamic stabilities of the mutants constructed at these positions. Surprisingly, our analysis of sequence alignment data provided a more accurate prediction of the stability of mutants than did examination of the three-dimensional structure of the domain.

Amino Acid Sequence↗
PubMed1999

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six Ser --> Ala mutants.

To further examine the contribution of hydrogen bonds to the conformational stability of the human lysozyme, six Ser to Ala mutants were constructed. The thermodynamic parameters for denaturation of these six Ser mutant proteins were investigated by differential scanning calorimetry (DSC), and the crystal structures were determined by X-ray analysis. The denaturation Gibbs energy (DeltaG) of the Ser mutant proteins was changed from 2.0 to -5.7 kJ/mol, compared to that of the wild-type protein. With an analysis in which some factors that affected the stability due to mutation were considered, the contribution of hydrogen bonds to the stability (Delta DeltaGHB) was extracted on the basis of the structures of the mutant proteins. The results showed that hydrogen bonds between protein atoms and between a protein atom and a water bound with the protein molecule favorably contribute to the protein stability. The net contribution of one intramolecular hydrogen bond to protein stability (DeltaGHB) was 8.9 +/- 2.6 kJ/mol on average. However, the contribution to the protein stability of hydrogen bonds between a protein atom and a bound water molecule was smaller than that for a bond between protein atoms.

Alanine↗
PubMed1999

Stability and folding of dihydrofolate reductase from the hyperthermophilic bacterium Thermotoga maritima.

Dihydrofolate reductase (DHFR) has been a well-established model system for protein folding. The enzyme DHFR from the hyperthermophilic bacterium Thermotoga maritima (TmDHFR) displays distinct adaptations toward high temperatures at the level of both structure and stability. The enzyme represents an extremely stable dimer; no isolated structured monomers could be detected in equilibrium or during unfolding. The equilibrium unfolding strictly follows the two-state model for a dimer (N(2) right harpoon over left harpoon 2U), with a free energy of stabilization of DeltaG = -142 +/- 10 kJ/mol at 15 degrees C. The two-state model is applicable over the whole temperature range (5-70 degrees C), yielding a DeltaG vs T profile with maximum stability at around 35 degrees C. There is no flattening of the stability profile. Instead, the enhanced thermostability is characterized by shifts toward higher overall stability and higher temperature of maximum stability. TmDHFR unfolds in a highly cooperative manner via a nativelike transition state without intermediates. The unfolding reaction is much slower (ca. 10(8) times) compared to DHFR from Escherichia coli (EcDHFR). In contrast to EcDHFR, no evidence for heterogeneity of the native state is detectable. Refolding proceeds via at least two intermediates and a burst-phase of rather low amplitude. Reassociation of monomeric intermediates is not rate-limiting on the folding pathway due to the high association constant of the dimer.

Bacterial Proteins↗
PubMedDate not supplied

Directed evolution of N-carbamyl-D-amino acid amidohydrolase for simultaneous improvement of oxidative and thermal stability.

Directed evolution of N-carbamyl-D-amino acid amidohydrolase from Agrobacterium tumefaciens NRRL B11291 was attempted in order to simultaneously improve oxidative and thermal stability. A mutant library was generated by DNA shuffling, and positive clones with improved oxidative and thermal stability were screened on the basis of the activity staining method on a solid agar plate containing pH indicator (phenol red) and substrate (N-carbamyl-D-p-hydroxyphenylglycine). Two rounds of directed evolution resulted in the best mutant 2S3 with a significantly improved stability. Oxidative stability of the evolved enzyme 2S3 was about 18-fold higher than that of the wild type, and it also showed an 8-fold increased thermostability. The K(m) value of 2S3 was comparable to that of wild-type enzyme, but k(cat) was slightly decreased. DNA sequence analysis revealed that six amino acid residues (Q23L, V40A, H58Y, G75S, M184L, and T262A) were substituted in 2S3. From the mutational analysis, four mutations (Q23L, H58Y, M184L, and T262A) were found to lead to an improvement of both oxidative and thermal stability. Of them, T262A had the most significant effect, and V40A and G75S only increased the oxidative stability.

Agrobacterium tumefaciens↗
PubMed2003

Impact of whey protein emulsifiers on the oxidative stability of salmon oil-in-water emulsions.

To obtain a better understanding of how the interfacial region of emulsion droplets influences lipid oxidation, the oxidative stability of salmon oil-in-water emulsions stabilized by whey protein isolate (WPI), sweet whey (SW), beta-lactoglobulin (beta-Lg), or alpha-lactalbumin (alpha-La) was evaluated. Studies on the influence of pH on lipid oxidation in WPI-stabilized emulsions showed that formation of lipid hydroperoxides and headspace propanal was much lower at pH values below the protein's isoelectric point (pI), at which the emulsion droplets were positively charged, compared to that at pH values above the pI, at which the emulsion droplets were negatively charged. This effect was likely due to the ability of positively charged emulsion droplets to repel cationic iron. In a comparison of lipid oxidation rates of WPI-, SW-, beta-Lg-, and alpha-La-stabilized emulsions at pH 3, the oxidative stability was in the order of beta-Lg > or = SW > alpha-La > or = WPI. The result indicated that it was possible to engineer emulsions with greater oxidative stability by using proteins as emulsifier, thereby reducing or eliminating the need for exogenous food antioxidants.

Drug Stability↗
PubMed2002

Oil stability prediction by high-resolution (13)C nuclear magnetic resonance spectroscopy.

(13)C NMR spectra of oil fractions obtained chromatographically from 66 vegetable oils were obtained and analyzed to evaluate the potential use of those fractions in predicting oil stabilities and to compare those results with oil stability prediction by using chemical determinations. The oils included the following: virgin olive oils from different cultivars and regions of Europe and north Africa; "lampante" olive, refined olive, refined olive pomace, low-erucic rapeseed, high-oleic sunflower, corn, grapeseed, soybean, and sunflower oils. Oils were analyzed for fatty acid and triacylglycerol composition, as well as for phenol and tocopherol contents. By using stepwise linear regression analysis (SLRA), the chemical determinations and the (13)C NMR data that better explained the oil stability determined by the Rancimat were selected. These selected variables were related to both the susceptibility of the oil to be oxidized and the content of minor components that most contributed to oil stability. Because (13)C NMR considered many more variables than those determined by chemical analysis, the predicted stabilities calculated by using NMR data were always better than those obtained by using chemical determinations. All these results suggest that (13)C NMR may be a powerful tool to predict oil stabilities when applied to chromatographically enriched oil fractions.

Corn Oil↗
PubMed2006

Oxidative stability of algal oils as affected by their minor components.

Algal oils, namely, arachidonic acid single-cell oil (ARASCO), docosahexaenoic acid single-cell oil (DHASCO), and a single-cell oil rich in both docosahexaenoic acid and docosapentaenoic acid (OMEGA-GOLD oil), were evaluated for their oxidative stability, as such and after stripping of their minor components, in the dark at 60 degrees C and under fluorescent light at 27 degrees C. Several analytical methods were used to assess the oxidative stability of these oils. Oil extracts were also investigated for their scavenging of 1,1-diphenyl-2-picrylhydrazyl radical by a spectrophotometric method and by measuring their total phenolic contents. The results indicated that minor oil constituents play a major role in their oxidative stability in the dark as well as under fluorescent light. The stability of the oils was dictated by their fatty acid composition, total tocopherols, and the type of pigment present. DHASCO contained a significant level of natural radical scavengers and phenolic compounds that contributed to its higher stability compared to the ARASCO and OMEGA-GOLD oils. Thus, the importance of minor components in the stability of the oils examined was demonstrated.

Arachidonic Acid↗
PubMed2006

Role of proteins in oil-in-water emulsions on the stability of lipid hydroperoxides.

The purpose of this research was to better understand the mechanisms by which proteins affect the rates of lipid oxidation in order to develop protein-stabilized emulsion delivery systems with maximal oxidative stability. This study evaluated the affect of pH and emulsifier concentration on the stability of cumene hydroperoxide in hexadecane-in-water emulsions stabilized by beta-lactoglobulin (beta-Lg). Emulsions prepared with 0.2 wt % beta-Lg (at pH 7.0) showed a 26.9% decrease in hydroperoxide concentrations 5 min after 0.25 mM ferrous ion was added to the emulsion. EDTA, but not continuous phase beta-Lg, could inhibit iron-promoted lipid hydroperoxide decomposition. Lipid hydroperoxides were more stable to iron-promoted degradation at pH values below the pI of beta-Lg, where the emulsion droplet would be cationic and thus able to repel iron away from the lipid hydroperoxides. Heating the beta-Lg-stabilized emulsions to produce a cohesive protein layer on the emulsion droplet surface did not alter the ability of iron to decompose lipid hydroperoxides. These results suggest that proteins at the interface of emulsion droplets primarily stabilize lipid hydroperoxides by electrostatically inhibiting iron-hydroperoxide interactions.

Alkanes↗
PubMed1996

Stabilization of tetanus toxoid in poly(DL-lactic-co-glycolic acid) microspheres for the controlled release of antigen.

Sustained release of antigenically active tetanus toxoid (TT) for several weeks from biodegradable poly (DL-lactic-co-glycolic acid) (PLGA) microspheres is very important for the development of a single dose vaccine. With a view to developing such a formulation, we evaluated in the vitro release of antigenic TT from TT-containing PLGA films and microspheres stabilized with gelatin or human serum albumin. Without stabilizer, TT-containing PLGA films released low levels of antigenic TT whereas TT-containing PLGA microspheres (average size 50 microMs) released 18% of antigenic TT in 4 weeks. Inclusion of gelatin and human serum albumin increased the amount of antigenic TT released from PLGA films and microspheres. As the concentration of gelatin increased from 0.08% to 2.2% in PLGA films, release of antigenic TT also increased. Similar results were found with gelatin-stabilized TT-containing microspheres. But the significant increase by higher concentration of gelatin was on the initial burst during the first week. A concentration of 0.2% gelatin was found suitable for getting approximately 40% of antigenic TT in 4 weeks. The proportion of antigenic TT to total protein was higher during the first 2 weeks of the release studies (50% during the first week and 23% during the second week). After 2 weeks, the proportion of antigenic TT was approximately 10% for the next 2 weeks. TT-containing microspheres stabilized with gelatin and human serum albumin showed stability of antigenic TT release when these microspheres were stored at 37 degrees C for 4 weeks. Gelatin appears to be a good stabilizer for TT-containing microspheres, but further studies are required to increase the proportion of antigenic TT beyond 2 weeks.

Antigens↗
PubMed1996

Aqueous stability of recombinant human thrombopoietin as a function of processing schemes.

Preformulation studies conducted with recombinant human thrombopoietin (rhTPO), a 332 amino acid glycoprotein which stimulates platelet production, show distinctions in degradation profiles as a function of processing schemes. The stability-limiting degradation pathways change as a function of purification stage and method and are dependent upon the presence of contaminating protease. The stability-limiting degradation pathway of affinity-purified and in-process rhTPO preparations is primarily attributed to proteolysis initiated by a protease present as a fermentation contaminant. The proteolysis increases with increasing pH as a function of temperature. The degradation profiles for these preparations show that bioactivity initially increases and then decreases with increasing pH as a function of temperature. This is consistent with proteolysis to active forms which ultimately undergo degradation to less active forms. Similar studies conducted with rhTPO preparations purified by a combination of more conventional chromatographic steps show different stability-limiting degradation pathways and a different pH-stability profile when compared to affinity purified or in-process preparations. In this case, degradation is accompanied by decreases in activity under all conditions, consistent with the conversion to less active forms. These results illustrate the importance of preformulation and stability characterization of protein pharmaceuticals in support of both process and formulation development. Issues related to storage and handling of inprocess preparations differ from those with formulated product since the stability-limiting degradation pathways change as a function of purification stage.

Animals↗
PubMed1998

Effects of various protease inhibitors on the stability and permeability of [D-Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.

The effects of various protease inhibitors on the stability of leucine enkephalin (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the permeability of these peptides was also examined in an in vitro Ussing chamber. Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in the stability of Leu-Enk and DADLE were observed, and the rank order of the stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC, amastatin, and puromycin were effective protease inhibitors for improving the stability of these peptides, although captopril and thiorphan did not improve the stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the intestinal membrane in the absence of protease inhibitors, but its transport was improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin improved the permeability of DADLE in both jejunum and colon, while the permeability of DADLE was not improved by the addition of captopril, thiorphan, and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly absorbable and stable compound, was also improved in the presence of Na-GC and bacitracin at a concentration of 10 mM. These findings indicated that amastatin, puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC and bacitracin at a concentration of 10 mM had absorption-enhancing activities which might be also related to the enhanced permeability of DADLE across the intestinal membrane.

Animals↗
PubMed1995

Hydroxypropyl-beta-cyclodextrin increases the aqueous solubility and stability of pilocarpine prodrugs.

PURPOSE: The effects of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were investigated at pH 7.4. METHODS: The solubility of prodrugs was studied by phase-solubility method (0-72.5 mM HP-beta-CD). The stability of one of the prodrugs was investigated as a function of temperature (40 degrees C-70 degrees C) and HP-beta-CD concentration (0-72.5 mM). The apparent rate constants (k1, k2) for degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability constants (K1:1, K1:2) were calculated by the curve-fitting method. RESULTS: The phase-solubility diagrams were classified as Ap-type and the apparent stability constants (K1:1, K1:2) for 1:1- and 1:2-inclusion complexes were calculated to be 143-815 M-1 and 29-825 M-1, respectively. The stability of prodrug increased as a function of HP-beta-CD concentration over the studied temperature range. The shelf-life (t90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM HP-beta-CD solution increased 5.1-fold and 6.1-fold at 25 degrees C and 4 degrees C, respectively. CONCLUSIONS: The solubility of the prodrugs was shown to increase markedly in phase-solubility studies. The degradation rate of prodrug in stability studies was shown to be slower in the 1:2-complex than in the 1:1-complex and the relative amounts of complex species were found to be dependent on CD concentration.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody.

PURPOSE: To study the effect of trehalose, lactose, and mannitol on the biochemical stability and aerosol performance of spray-dried powders of an anti-IgE humanized monoclonal antibody. METHODS: Protein aggregation of spray-dried powders stored at various temperature and relative humidity conditions was assayed by size exclusion chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein glycation was determined by isoelectric focusing and affinity chromatography. Crystallization was examined by X-ray powder diffraction. Aerosol performance was assessed as the fine particle fraction (FPF) of the powders blended with coarse carrier lactose, and was determined using a multiple stage liquid impinger. RESULTS: Soluble protein aggregation consisting of non-covalent and disulfide-linked covalent dimers and trimers occurred during storage. Aggregate was minimized by formulation with trehalose at or above a molar ratio in the range of 300: 1 to 500:1 (excipient:protein). However, the powders were excessively cohesive and unsuitable for aerosol administration. Lactose had a similar stabilizing effect, and the powders exhibited acceptable aerosol performance, but protein glycation was observed during storage. The addition of mannitol also reduced aggregation, while maintaining the FPF, but only up to a molar ratio of 200:1. Further increased mannitol resulted in crystallization, which had a detrimental effect on protein stability and aerosol performance. CONCLUSIONS: Protein stability was improved by formulation with carbohydrate. However, a balance must be achieved between the addition of enough stabilizer to improve protein biochemical stability without compromising blended powder aerosol performance.

Aerosols↗
PubMed2004

Reciprocal regulation of beta-adrenergic receptor mRNA stability by mitogen activated protein kinase activation and inhibition.

Genes encoding numerous proto-oncogenes and cytokines, as well as a number of G-protein coupled receptors, are regulated post-transcriptionally at the level of mRNA stability. A common feature of all of these genes is the presence of A + U-rich elements (AREs) within their 3' untranslated regions. We, and others, have demonstrated previously that mRNAs encoding beta-adrenergic receptors (beta-ARs) are destabilized by agonist stimulation of the beta-AR/Galphas/adenylylcyclase pathway. However, in addition to PK-A, beta-ARs can also activate or inhibit mitogen activated kinase (MAPK) cascades, in a cell-type dependent basis. Recent evidence points to an important role for MAPKs in regulating the turnover of cytokine mRNAs, such as TNFalpha. We hypothesized that activation of MAPK's may also regulate beta-AR mRNA stability. The studies conducted herein demonstrate that generalized stimulation of MAPKs (JNK, p38) with anisomycin resulted in marked stabilization of beta-AR mRNA. Reciprocally, selective inhibition of JNK with SP600125 significantly decreased beta-AR mRNA half-life. Similarly, inhibition of the MEK/ERK pathway with either PD98059 or U0126 decreased beta-AR mRNA stability substantially. However, inhibition of p38 MAPK with SB203580 produced destabilization of beta-AR mRNA only at higher, non pharmacologically selective concentrations. In contrast to their effects on several other ARE containing mRNAs, inhibition of tyrosine kinases by genistein or PI3K by wortmannin, had no detectable effect on beta-AR mRNA stability. In summary, these results demonstrate for the first time that modulation of MAPK pathways can bi-directionally influence beta-AR mRNA stability.

3' Untranslated Regions↗
PubMed2003

Improved alpha-chymotrypsin stability upon encapsulation in PLGA microspheres by solvent replacement.

PURPOSE: To investigate the potential of different solvents with better biocompatibility to replace CH2Cl2 in the encapsulation of alpha-chymotrypsin in poly (lactic-co-glycolic) acid (PLGA) microspheres without causing protein instability. METHODS: The oil-to-water (O:W) ratio in the emulsification step of the solid-in-oil-in-water (s/o/w) encapsulation process was optimized with respect to maximizing protein stability and encapsulation efficiency for various solvents. Formation of insoluble aggregates and residual enzyme activity were primarily used as stability parameters. Several solvents possessing low toxicity with different water solubility were used to prepare alpha-chymotrypsin loaded PLGA microspheres. RESULTS: The O:W ratio in the emulsification step is critical with respect to maintaining protein stability. This was related to the solvents' water solubility. In general, hydrophilic solvents were detrimental to protein stability and encapsulation efficiency. However, after optimization of the O:W ratio for solvents with different water solubility, protein stability was preserved during encapsulation using butyl acetate when poly (ethylene glycol) (PEG) was used as the emulsifying agent (ca. 1% of non-covalent aggregates and 93 +/- 10% of residual specific activity). CONCLUSIONS: The s/o/w technique was successfully improved by replacing the ICH class 2 solvent CH2Cl2 with the class 3 solvent butyl acetate without compromising alpha-chymotrypsin stability.

Chymotrypsin↗
PubMed2004

Identification of stabilized dynorphin derivatives for suppressing tolerance in morphine-dependent rats.

PURPOSE: Modulatory actions on morphine-induced effects, such as tolerance and withdrawal, have been noted for dynorphin A(1-13) [Dyn A(1-13)] and similar peptides. These are currently of limited therapeutic potential due to extensive metabolism by human metabolic enzymes resulting in a half-life of less than 1 min in human plasma. The purpose of this study was to identify stabilized dynorphin A (Dyn A) derivatives, to determine their metabolic routes in human plasma, and to assess whether the pharmacodynamic activity is retained. METHODS: The stability of peptides in human plasma was tested using in vitro metabolism studies with and without enzyme inhibitors. Identification of the generated metabolites was performed by mass spectrometry after high performance liquid chromatography (HPLC) separation. The in vivo activity of a stabilized dynorphin was tested by tail-flick assay in morphine-tolerant rats. RESULTS: Though amidation of the Dyn A(1-13) was able to stop the majority of C-terminal degradation, metabolism of Dyn A(1-10) amide continued by captopril sensitive enzymes, suggesting that Dyn A(1-13) amide is a better candidate for additional stabilization. Two Dyn A(1-13) amide derivatives further stabilized at the N-terminal end, [D-Tyr1]-Dyn A(1-13) amide and [N-Met-Tyr1]-Dyn A(1-13) amide, showed half-lives in plasma of 70 and 130 min, respectively. The most stable derivative [N-Met-Tyr1]-Dyn A(1-13) amide was tested successfully for retention of the pharmacological activity in modulating antinociceptive activity. CONCLUSIONS: [N-Met-Tyr1]-Dyn A(1-13) amide showed significant stability and antinociceptive activity in the tail-flick test, thus pointing to the clinical potential of this derivative in the management of pain as well as its potential activity in suppressing opiate tolerance and withdrawal.

Aminopeptidases↗
PubMed2004

Design and evaluation of an emulsion vehicle for paclitaxel. I. Physicochemical properties and plasma stability.

PURPOSE: The current formulation of paclitaxel contains ethanol and Cremophor EL and has been reported to cause serious adverse reactions. The purpose of the present work was to develop an improved emulsion vehicle for paclitaxel and to study the physicochemical properties of such a system. METHODS: Emulsions were prepared by either microfluidization or sonication method and the droplet size characterized by dynamic light scattering and light microscopy. RESULTS: Stable emulsions could be made using mixtures of lecithin/sodium deoxycholate as the emulsifiers. The formulation was further improved by using a combination of free acid and the sodium salt. Paclitaxel could be loaded into the emulsions at 2.5 mg/ml without the formation of drug crystals. While these emulsions were stable on storage, they flocculated when mixed with plasma. Steric stabilization of the emulsion droplets with poloxamer 188 increased the stability of the emulsions in plasma but promoted the crystallization of paclitaxel. The crystallization tendency could be reduced by using PEG5000PE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[poly (ethylene glycol) 5000]), a less water-soluble stabilizer. CONCLUSIONS: Emulsions with good stability characteristics containing 2.5 mg/ml paclitaxel could be made using bile salt/acid and lecithin, and the excellent stability of these emulsions in plasma was achieved by steric stabilization using PEG5000PE.

Animals↗