A glucose-sensitive microcapsule with a porous membrane and with linear-grafted polyacrylic acid (PAAC) chains and covalently bound glucose oxidase (GOD) enzymes in the membrane pores acting as functional gates was successfully prepared. Polyamide microcapsules with a porous membrane were prepared by interfacial polymerization, PAAC chains were grafted into the pores of the microcapsule membrane by plasma-graft pore-filling polymerization, and GOD enzymes were immobilized onto the PAAC-grafted microcapsules by a carbodiimide method. The release rates of model drug solutes from the fabricated microcapsules were significantly sensitive to the existence of glucose in the environmental solution. In solution, the release rate of either sodium chloride or VB(12) molecules from the microcapsules was low but increased dramatically in the presence of 0.2mol/L glucose. The prepared PAAC-grafted and GOD-immobilized microcapsules showed a reversible glucose-sensitive release characteristic. The proposed microcapsules provide a new mode for injection-type self-regulated drug delivery systems having the capability of adapting the release rate of drugs such as insulin in response to changes in glucose concentration, which is highly attractive for diabetes therapy. 相似文献
Alogliptin (ALG) is a hypoglycemic drug used in diabetes which inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), preventing the degradation of incretins, stimulating insulin secretion. The physicochemical characteristics of ALG were evaluated by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy equipped with energy-dispersive X-ray spectrometer (SEM/EDS). The compatibility studies were carried out between ALG and excipients (physical mixtures, 1:1) using DSC, TG, diffuse reflectance Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and hot-stage microscopy. ALG presented purity near to 99%, melted in the range of 179.4–187.2 °C, followed by decomposition which started in 198.0 °C. SEM/EMS analysis of ALG presented irregular crystals and traces of impurities as copper and lead. DSC investigations obtained by physical mixtures showed minor alterations in the melting ranges of ALG with mannitol, magnesium stearate and commercial tablets. Solubilization of ALG in the fused excipient was observed by hot-stage microscopy between mannitol and ALG, and in tablets. The interaction observed in the mixture with magnesium stearate is due to the melting of the excipient and drug separately, first the excipient and then the drug. FTIR showed additional bands related to the excipients. XRPD proved that ALG has a crystal form and no alterations in the ALG profile were observed after the mixtures. ALG was compatible with all excipients tested. These results were important to understand the characteristics, stability and compatibility of the drug, and proved to be useful in preformulation studies.
Loading and release characteristics of insulin-carrying albumin and starch microspheres have been studied in vitro. The sorption characteristics of 125I-labelled insulin onto albumin microspheres were studied and were found to be completed within 5h, and the loading capacity was found to be 0.14% w/w. Insulin did not show any sorption into the matrix of the starch microspheres. The release characteristics were analyzed by high performance liquid chromatography. About 80% was released within 5-10 min from albumin microspheres and starch microspheres, respectively. 相似文献
Summary: Environmentally responsive hydrogels composed of poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) have shown promise for oral insulin delivery due to their pH responsive complexation behavior. A series of hydrogel formulations were polymerized with varying amounts of crosslinker and varying monomer volume fraction. The mesh size of the network depended primarily on pH, varying from 8.0 to 27.2 nm. Insulin loading efficiency varied directly with crosslink density, ranging from 42.7 to 84.9% of available insulin loaded into the hydrogels. The release of insulin was performed with each polymer formulation at 5 pH levels ranging from 2.7 to 6.8. Insulin release was less than 20% for all formulations tested with insulin for the duration of the 3 hour release study for all pH levels considered except when the pH was 6.8, at which point the release occurred as a burst. Loading studies performed with insulin glargine, an insulin analog with an increased pI, showed the same trends as native insulin. However, the release of insulin glargine only occurred at a pH level above that of the pI of the protein. These results indicate that hydrogen bonds and ionic interactions between the protein and P(MAA-g-EG) may strongly influence its loading and release behavior in vitro. 相似文献
Formation of stable thin films of mixed xyloglucan (XG) and alginate (ALG) onto Si/SiO(2) wafers was achieved under pH 11.6, 50mM CaCl(2), and at 70 degrees C. XG-ALG films presented mean thickness of (16+/-2)nm and globules rich surface, as evidenced by means of ellipsometry and atomic force microscopy (AFM), respectively. The adsorption of two glucose/mannose-binding seed (Canavalia ensiformis and Dioclea altissima) lectins, coded here as ConA and DAlt, onto XG-ALG surfaces took place under pH 5. Under this condition both lectins present positive net charge. ConA and DAlt adsorbed irreversibly onto XG-ALG forming homogenous monolayers approximately (4+/-1)nm thick. Lectins adsorption was mainly driven by electrostatic interaction between lectins positively charged residues and carboxylated (negatively charged) ALG groups. Adhesion of four serotypes of dengue virus, DENV (1-4), particles to XG-ALG surfaces were observed by ellipsometry and AFM. The attachment of dengue particles onto XG-ALG films might be mediated by (i) H bonding between E protein (located at virus particle surface) polar residues and hydroxyl groups present on XG-ALG surfaces and (ii) electrostatic interaction between E protein positively charged residues and ALG carboxylic groups. DENV-4 serotype presented the weakest adsorption onto XG-ALG surfaces, indicating that E protein on DENV-4 surface presents net charge (amino acid sequence) different from E proteins of other serotypes. All four DENV particles serotypes adsorbed similarly onto lectin films adsorbed. Nevertheless, the addition of 0.005mol/L of mannose prevented dengue particles from adsorbing onto lectin films. XG-ALG and lectin layers serve as potential materials for the development of diagnostic methods for dengue. 相似文献
Fe-immobilized polyelectrolyte microshells have been successfully constructed by alternative adsorption of Fe(III) and alginate sodium (ALG) onto the precursor shells composed of chitosan (CHI) and ALG templated on melamine formaldehyde (MF) particles. Confocal laser scanning microscopy (CLSM) directly demonstrated that the as-synthesized (ALG/CHI)4(ALG/Fe)n (n = 1, 2) shells could accumulate efficiently rhodamine B (RhB), methylene blue (MB) and acridine orange (AO) in well-defined internal space under moderate conditions via a simple mix processing. Further, H2O2 could cross the Fe-immobilized shell walls and react with the dyes concentrated in the interior of shells under visible radiation. The photodegradation of dyes accumulated in the microshells in the presence of H2O2 was characterized by UV–vis adsorption spectra and CLSM. More importantly, the photooxidative reaction occurring in the Fe-immobilized microshells can be performed at a wide range of pH from acid to neutral media, which is superior to the conventional Fenton reaction that allows taking effect only under acid condition of pH <4. Electron paramagnetic resonance (EPR) and other studies into the mechanism of the light-activated reaction process give tentative evidence that distinct from the photoreaction occurring in neutral medium, the photoreaction taking place in confined microshells in acid medium proceeds mainly through HO radicals with high oxidative potential. 相似文献
<正>A membrane composed of an alginate(ALG) layer and a chitosan(CHS) layer with sustained antimicrobial efficacy was prepared.Ciprofloxacin HC1(CIP) was incorporated into the ALG layer.Morphological feature of the composite membrane was analyzed by scanning electron microscopy(SEM).Water uptake capacity,in vitro drug release,and in vitro antimicrobial activity were evaluated.The composite membrane exhibited perfect binding characteristic between the two layers.The water uptake capacity of all the membranes was above 800%.The CIP could release from the composite membranes for 48 h.The membrane could control the bacterial growth persistently.The results suggested that this CHS/ALG composite membrane incorporated with CIP had the potential for wound dressing application. 相似文献
In this work, the producing of a biodegradable poly(l-lactide) (PLA)/poly(ethylene glycol) (PEG) microcapsule by emulsion solvent evaporation method was investigated. The effect of PEG segments added to the PLA microcapsules on the degradation, size distribution, and release behavior was studied. According to the results, PLA/PEG copolymer was more hydrophilic than PLA homopolymer, and with lower glass transition temperature. The surface of PLA/PEG microcapsules was not as smooth as that of PLA microcapsules, the mean diameters of prepared PLA and PLA/PEG microcapsules were 40 and 57 microm, respectively. And spherical forms were observed by the image analyzer and the scanning electron microscope (SEM). Drug release from microcapsules was affected by the properties of PLA/PEG copolymers determined by UV-vis spectra. It was found that the drug release rates of the microcapsules were significantly increased with adding of PEG, which explained by increasing hydrophilic groups. 相似文献
Nanoparticles have been prepared by dispersion polymerisation of n-butyl cyanoacrylate in acidified water, with and without the inclusion of insulin. The molecular weight of the polymerising material increases by a stepwise process, in which chains are initiated, terminated, and reinitiated, until an equilibrium molecular weight is reached. This equilibrium molecular weight is higher at lower dispersion pH. The reaction is complete within two hours. Insulin is capable of initiating polymerisation, but if introduced after all of the monomer has been incorporated into the growing nanoparticles it has no effect on polymer molecular weight. A drug loading of 72% was achieved in particles produced at 25 °C and pH 3.0, with insulin introduced one hour after monomer initiation. Particle degradation characteristics were assessed using solutions of esterase in phosphate buffered saline at pH 7.0, with butanol release monitored as a measure of polymer degradation. Insulin release was monitored under the same conditions. Both butanol production and insulin release showed a similar biphasic mechanism, indicating that the drug release rate is determined by polymer degradation characteristics. An initial burst release of both materials is associated with the degradation of surface species, and this is then followed by a steady-state release from sub-surface material.
Insulin release as a function of time at an esterase concentration of 2.0 mg · ml−1. 相似文献
Insulin and its analogues have been banned in both human and equine sports owing to their potential for misuse. Insulin administration can increase muscle glycogen by utilising hyperinsulinaemic clamps prior to sports events or during the recovery phases, and increase muscle size by its chalonic action to inhibit protein breakdown. In order to control insulin abuse in equine sports, a method to effectively detect the use of insulins in horses is required. Besides the readily available human insulin and its synthetic analogues, structurally similar insulins from other species can also be used as doping agents. The author's laboratory has previously reported a method for the detection of bovine, porcine and human insulins, as well as the synthetic analogues Humalog (Lispro) and Novolog (Aspart) in equine plasma. This study describes a complementary method for the simultaneous detection of five exogenous insulins and their possible metabolites in equine urine. Insulins and their possible metabolites were isolated from equine urine by immunoaffinity purification, and analysed by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS). Insulin and its analogues were detected and confirmed by comparing their retention times and major product ions. All five insulins (human insulin, Humalog, Novolog, bovine insulin and porcine insulin), which are exogenous in horse, could be detected and confirmed at 0.05ng/mL. This method was successfully applied to confirm the presence of human insulin in urine collected from horses up to 4h after having been administered a single low dose of recombinant human insulin (Humulin R, Eli Lilly). To our knowledge, this is the first identification of exogenous insulin in post-administration horse urine samples. 相似文献
Numerous microcapsule systems have been developed for a wide range of applications, including the sustained release of drugs, cell transplantation for therapy, cell immobilization, and other biotechnological applications. Despite the fact that microcapsule membrane is a dominant factor governing overall microcapsule performance, its characterization is challenging. We report a new method for characterizing microcapsule membranes, using the most common alginate-poly-L-lysine-alginate (APA) microcapsule as an example. Our data demonstrate that genipin, a naturally derived reagent extracted from gardenia fruits, interacts with poly-L-lysine (PLL) and generates fluorescence. This fluorescence allows clear visualization and easy analysis of the PLL membrane in the APA microcapsules using confocal laser scanning microscopy. The results also show that PLL binding correlates to the reaction variables during PLL coating such as PLL concentration and coating time. In addition, five other different microcapsule formulations consisting of PLL and/or chitosan membranes were examined, and the results imply that this method can be extended to characterize a variety of microcapsule membranes. These findings suggest that genipin can serve as a fluorogenic marker for rapid characterization of microcapsule membranes, a superior method that would have important implications for microcapsule research and potential in many other applications. 相似文献
Biodegradable oligolysine and oligoarginine-type homopeptides functionalized with PEG of two different molecular weights interact with insulin, at physiological pH, affording complexes studied by dynamic light scattering, ζ-potential, circular dichroism, FTIR spectroscopy, and isothermal titration calorimetry (ITC). High levels of insulin complexation efficiencies (>99.5%) were determined for all derivatives. FTIR spectra suggest that the positively charged homo-oligopeptide derivatives interact with B chain C-terminus of insulin leading to the formation of nanoparticles than can be traced even at low oligopeptide/insulin molar ratios. The ITC profiles are complex, displaying significant endothermic and exothermic contributions. Oligoarginine-type derivatives exhibit the strongest interactions, while PEGylation of either oligopeptide with the high molecular weight chains significantly affects the ITC profiles and leads to larger enthalpy changes. This may be attributed to PEG-induced aggregation of insulin due to the depletion attraction effect leading to the formation of stable nanocomplexes. Stabilization of complexed insulin against enzymatic degradation by trypsin and α-chymotrypsin is observed especially for the high molecular weight PEGylated arginine-based derivative. Insulin release rates in simulated intestinal fluid are controlled by the length of PEG chains and the presence of arginine end-groups. Released insulin retains its secondary structure as established by circular dichroism spectroscopy. 相似文献
Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique. Insulin, a model protein, was successfully loaded into microparticles by changing experimental variables such as polymer molecular weight, polymer concentration, surfactant concentration and stirring speed in order to optimize process variables on drug encapsulation efficiency, release rates, size and size distribution. A 24 full factorial design was employed to evaluate systematically the combined effect of variables on responses. Scanning electron microscope (SEM) confirmed spherical shapes, smooth surface morphology and microsphere structure without aggregation. FTIR and DSC results showed drug–polymer interaction. The encapsulation efficiency of insulin was mainly influenced by surfactant concentration. Moreover, polymer concentration and polymer molecular weight affected burst release of drug and size characteristics of microspheres, respectively. It was concluded that using PLGA with higher molecular weight, high surfactant and polymer concentrations led to a more appropriate encapsulation efficiency of insulin with low burst effect and desirable release pattern. 相似文献
Numerous microcapsule systems have been developed for a wide range of applications, including the sustained release of drugs,
cell transplantation for therapy, cell immobilization, and other biotechnological applications. Despite the fact that microcapsule
membrane is a dominant factor governing overall microcapsule performance, its characterization is challenging. We report a
new method for characterizing microcapsule membranes, using the most common alginate-poly-l-lysine-alginate (APA) microcapsule as an example. Our data demonstrate that genipin, a naturally derived reagent extracted
from gardenia fruits, interacts with poly-l-lysine (PLL) and generates fluorescence. This fluorescence allows clear visualization and easy analysis of the PLL membrane
in the APA microcapsules using confocal laser scanning microscopy. The results also show that PLL binding correlates to the
reaction variables during PLL coating such as PLL concentration and coating time. In addition, five other different microcapsule
formulations consisting of PLL and/or chitosan membranes were examined, and the results imply that this method can be extended
to characterize a variety of microcapsule membranes. These findings suggest that genipin can serve as a fluorogenic marker
for rapid characterization of microcapsule membranes, a superior method that would have important implications for microcapsule
research and potential in many other applications. 相似文献
Electrospray has been recognized as an efficient technique for the fabrication of polymer micro and nanosystems and recently it was applied to lipids. The objective of this study was to assess the potential of electrospray for the encapsulation of insulin into lipid particles. Spherical particles of about 1 µm were obtained jetting a propanolic solution of palmitic or stearic acid and ethylcellulose or Pluronic F127 in a 10:1 or 20:1 (w/w) ratio under an electric field of 30 kV. Insulin was entrapped into the particles with high encapsulation efficiency by the formation of an ion-pair with sodium dodecyl sulphate. Far-ultraviolet circular dichroism spectroscopy indicated that electrospray did not modify the secondary structure of insulin. An in vitro prolonged release over 24 hours was observed after an initial burst effect. This study demonstrates that electrospray represents a viable new alternative for preparing in a single step peptide-protein loaded lipid based microspheres directly in powder form. 相似文献