Preparation, Post-Modification, and Antibacterial Application of Gelatin Electrospun Membranes.

Two bis(diaryldiazomethane)s substituted with amino groups are synthesized and used for the surface modification of membranes electrospun from gelatin. These membranes are then reacted with tolylene-2,4-diisocyanate to give urea-functionalized materials, so that hydrogen peroxide can be reversibly bound onto their surface. These membranes are characterized by scanning electron microscopy, XPS, differential scanning calorimeter, and tensile test to show their surface properties and bulk properties. The surface modification with amino-substituted diazomethanes and the subsequent cross-linking reaction with diisocyanates contribute to high loadings of hydrogen peroxide, and greatly increase the antibacterial activity of gelatin-derived membranes, which open a new horizon in the preparation of high loading antiseptic/antibacterial biomacromolecular surfaces and interfaces.

Polymerizable-group capped ZnS nanoparticle for high refractive index inorganic-organic hydrogel contact lens.

Refractive index (RI) is an important parameter for contact lens biomaterials. In this paper, a novel polymerizable-group capped ZnS nanoparticle (NP) was synthesized by chemical link between hydroxyl group on the surface of ZnS (ME-capped) and isocyanate group of polymerizable molecule of 2-isocyanatoethyl methacrylate. Then the ZnS NP copolymerized with monomer of 2-hydroxyethyl methacrylate (HEMA) and N,N-dimethylacrylamide (DMA) to prepare high refractive index hydrogel contact lens with high content of inorganic ZnS NP. Increasing polymerizable-group capped ZnS content in the hydrogels improved its RI value and mechanical properties, however decreased slightly its transmittance, equilibrium (ESR) and lysozyme deposition on the hydrogel surface. The ZnS-containing hydrogels possessed good cytocompatibility and in vivo biocompatibility in rabbit eyes, demonstrating a potential application as high RI ocular refractive correction biomaterial.

Preparation and Photoluminescence of Transparent Poly(methyl methacrylate)-Based Nanocomposite Films with Ultra-High-Loading Pendant ZnS Quantum Dots.

Transparent nanocomposite films containing quantum dots are popular because of their extensive applications. However, nanoparticles tend to aggregate, resulting in phase separation of the nanoparticles in the polymer matrix. Herein, we present a bulk thermo-curing copolymerization method to fabricate poly(methyl methacrylate)-based nanocomposite films with ultra-high-loading ZnS quantum dots (ZnS/PMMA), utilizing polymerizable group-capped ZnS and monomer of methyl methacrylate (MMA). We found that the nanocomposite film is highly transparent, although the transmittance decreases with the ZnS content, especially at the wavelength between 300 nm and 400 nm. The results from X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic mechanical thermal analysis (DMTA) show that the ZnS quantum dots maintain their original crystal structure, and are uniformly dispersed in the nanocomposite films, even with a very high ZnS content (41 wt %, determined by thermogravimetric analysis). The thermogravimetric analysis shows that the nanocomposite films possess a better thermal stability than that of pure PMMA film. The photoluminescence measurements show that ZnS/PMMA nanocomposite films have good optical properties. The fluorescence intensity increases with the increment of free ZnS content to 30 wt %, and then decreases due to self-reabsorption at a higher ZnS content. The transparent ZnS/PMMA nanocomposite films have a potential application as photoluminescence material.

Electrospun Gelatin Membrane Cross-Linked by a Bis(diarylcarbene) for Oil/Water Separation: A New Strategy To Prepare Porous Organic Polymers.

Porous organic polymers (POPs) as absorbing materials have attracted increasing attention. Here, we report a new approach to prepare these polymers for selective oil absorption from oil/water mixtures. Perfluoroalkylbis(diaryldiazomethane) was synthesized and used to modify the surface of an electrospun gelatin membrane by a carbene insertion reaction, not only to immobilize the porous network morphology by cross-linking but also to introduce perfluoroalkyl groups for oil/water separation. The membrane was characterized to show its surface and bulk properties, as well as its performance for absorption capacity, selectivity, and renewability. This approach offers a new horizon in the preparation of POPs for oil/water separation.

Iodine-responsive poly (HEMA-PVP) hydrogel for self-regulating burst-free extended release.

Swollen hydrogels with extended iodine release kinetics is highly desirable for burn and scald treatment. In this paper semi-interpenetrating poly (HEMA-PVP) hydrogels were prepared by radical polymerization followed by thermo-treatment to crosslink its PVP component. Incorporation of PVP component endows the hydrogels responsive to loaded iodine undergoing a reversible shrunken/swollen volume transition. This resulted in a self-regulating iodine release model, in which shrunken hydrogel at high iodine loading decreased drug diffusion thereby reducing burst release, and then gradually swollen hydrogel as drug release ensures rapid release of dissociated drug from strong affinity sites on hydrogel backbone, achieving a burst-free extended release. The hydrogels demonstrated 11.5-fold higher iodine loading than pure pHEMA hydrogel and showed a highest 40% volume shrink. Initial burst release of iodine was efficiently decreased from 12,894 µg/day of pure pHEMA hydrogel to 2570 µg/day of pHEMA/PVP hydrogel with 37% PVP content. Iodine-loaded hydrogels showed zero-order release at three time periods of 0-15 h, 15 h-3.5 days and 3.5-23.5 days corresponding to release rate of 2570, 776 and 493 µg/day. The work gained a new insight into swollen hydrogel drug delivery system with burst-free extended drug release kinetics.

Electrospun N-Substituted Polyurethane Membranes with Self-Healing Ability for Self-Cleaning and Oil/Water Separation.

Membranes with special functionalities, such as self-cleaning, especially those for oil/water separation, have attracted much attention due to their wide applications. However, they are difficult to recycle and reuse after being damaged. Herein, we put forward a new N-substituted polyurethane membrane concept with self-healing ability to address this challenge. The membrane obtained by electrospinning has a self-cleaning surface with an excellent self-healing ability. Importantly, by tuning the membrane composition, the membrane exhibits different wettability for effective separation of oil/water mixtures and water-in-oil emulsions, whilst still displaying a self-healing ability and durability against damage. To the best of our knowledge, this is the first report to demonstrate a self-healing membrane for oil/water separation, which provides the fundamental research for the development of advanced oil/water separation materials.

A simple and convenient method to synthesize N-[(2-hydroxyl)-propyl-3-trimethylammonium] chitosan chloride in an ionic liquid.

N-[(2-Hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride (HTCC) was synthesized through nucleophilic substitution of 2,3-epoxypropyltrimethyl ammonium chloride (EPTAC) onto chitosan using ionic liquid of 1-allyl-3-methylimidazole chloride (AmimCl) as a homogeneous and green reaction media. The chemical structure of HTCC was confirmed by FTIR, (1)H NMR and (13)C NMR. The FTIR peak intensity of amino group at 1595 cm(-1) decreased and that of [Formula: see text] at 1475 cm(-1) increased with the increase of reaction time, confirming the substitution of EPTAC on CS. The degree of substitutions (DS) were calculated from the integral area of (1)H NMR, and the optimum reaction condition was obtained, namely, reaction time of 8h, temperature of 80°C and [Formula: see text] of 3/1. The degree of crystallinity and thermal properties of HTCC were characterized by XRD, TG, DSC, and DMA methods. Data from XRD, TG, DSC and DMA show that the degree of crystallinity, thermal stability, as well as glass transition temperature of HTCC decreased with the increase of DS. The reaction mechanism of chitosan with EPTAC in AmimCl was elucidated by performing density functional theory (DFT) calculations.

Simultaneous interpenetrating silicone hydrogel based on radical/addition polymerization for extended release of ocular therapeutics.

Hydrogels with interpenetrating network (IPN) can overcome thermodynamic incompatibility and obtain transparent materials with limited phase separation. In this report, hydroxyl-grafting polysiloxane (HPSO) was synthesized and transparent silicone hydrogels with interpenetrating network were simultaneously prepared based on radical polymerization of methacrylic monomer of 3-methacryloxypropyl tris(trimethylsiloxy)silane/N,N-dimethylacrylamide and addition polymerization of HPSO/isophorone diisocyanate. The silicone hydrogels were characterized by dehydration kinetics, tensile tester, light transmittance, ion permeability, oxygen permeability, and lysozyme deposition. The results show that increasing the proportion of hydrophobic network of HPSO in the IPN silicone hydrogel decreases equilibrium swelling ratio, ion permeability, Young's modulus, and lysozyme deposition; on the contrary, increased tensile strength, elongation at break and oxygen permeability. Puerarin and ketoconazole were used as models to evaluate the drug loading and in vitro release behavior of the silicone hydrogels. It is revealed that the amount of loaded drugs in the hydrogel decreases with the increase of HPSO network in the hydrogels. All the silicone hydrogels exhibit extended release behavior, especially for ketoconazole, the in vitro release is divided into two phases corresponding to the rapid release at initial 24 h and relatively slow release from 125 to 360 h.

In vitro and in vivo evaluation of ketotifen fumarate-loaded silicone hydrogel contact lenses for ocular drug delivery.

The purpose of this work was to evaluate the usefulness of silicone hydrogel contact lenses loaded with ketotifen fumarate for ocular drug delivery. First, silicone contact lenses were prepared by photopolymerization of bitelechelic methacrylated polydimethylsiloxanes macromonomer, 3-methacryloxypropyltris(trimethylsiloxy)silane, and N,N-dimethylacrylamide using ethylene glycol dimethacrylate as a cross-linker and Darocur 1173 as an initiator followed by surface plasma treatment. Then, the silicone hydrogel matrices of the contact lenses were characterized by equilibrium swelling ratio (ESR), tensile tests, ion permeability, and surface contact angle. Finally, the contact lenses were loaded with ketotifen fumarate by pre-soaking in drug solution to evaluate drug loading capacity, in vitro and in vivo release behavior of the silicone contact lenses. The results showed that ESR and ion permeability increase, and the surface contact angle and tensile strength decreased with the increase of DMA component in the silicone hydrogel. The drug loading and in vitro releases were dependent on the hydrogel composition of hydrophilic/hydrophobic phase of the contact lenses. In rabbit eyes, the pre-soaked contact lenses sustained ketotifen fumarate release for more than 24 h, which leads to a more stable drug concentration and a longer mean retention time in tear fluid than that of eye drops of 0.05%.

PVA hydrogels containing beta-cyclodextrin for enhanced loading and sustained release of ocular therapeutics.

The purpose of this work is to develop poly(vinyl alcohol) (PVA) hydrogels incorporating large amounts of beta-cyclodextrin (beta-CD) in order to improve ocular drug loading and to sustain drug release. First, the mono-methacrylated-beta-CD monomer (MA-beta-CD) and the methacrylated-PVA macromer (PVAMA), with a substitution degree of 7%, are synthesized and characterized. Then, the poly(methacrylated-PVA-co-mono-methacrylated-beta-cyclodextrin) (pPVA-beta-CD) hydrogels are prepared by UV-induced polymerization of MA-beta-CD and PVAMA. The highest amount of beta-CD incorporated into the hydrogels is 30 wt%. The hydrogels are further characterized by transmittance, FT-IR, equilibrium swelling ratio (ESR), tensile tests and protein deposition. The results show that pPVA-beta-CD hydrogels possess good transmittance, while the incorporation of beta-CD in the hydrogels improves the tensile strength and decreases the ESR and protein deposition. Finally, puerarin and acetazolamide are used as models to evaluate the drug loading and in vitro release behavior of the pPVA-beta-CD hydrogels. The results indicate that the amount of drug loaded into the pPVA-beta-CD hydrogels progressively increases, while the release rate decreases with increasing beta-CD content. In particular, incorporation of beta-CD efficiently decreases the initial burst release of acetazolamide, while the release, which is almost linear, is sustained for 15 days. The pPVA-beta-CD hydrogels have potential applications as biomedical devices for sustained release of ocular drugs.

[Preparation and lacrimal pharmacokinetics of eye drops of puerarin liposomes in rabbit tears].

OBJECTIVE: To prepare eye drops of puerarin liposomes and investigate its lacrimal pharmacokinetics in rabbit tears. METHOD: Puerarin liposomes were prepared by reverse phase evaporation technique. The liposomes and free puerarin were separated by SephadexG-50 chromatography and then encapsulation ratio of liposomes was determined in detail. Micromorphology of liposome particles was observed by electronic transmission microscope and the size distribution of the liposomes was analyzed by laser particle size analyzer. The concentration of puerarin in rabbit's tears was determined by HPLC after ocular administration of 50 microL puerarin liposomes while puerarin eye drops was chosen as control with the same puerarin concentration. The pharmacokinetic parameters were calculated by software program 3P97 according to one-compartment mode. RESULT: Global liposome nanoparticles with diameter of about 195.7 nm were prepared successfully. The encapsulation ratio of puerarin in the liposomes was 48.3%. The mean residence time (MRT) value and the area under concentration (AUC) of puerarin in liposome were 3.89 and 3.06 times more than those of puerarin eye drops. CONCLUSION: Liposomes as a drug carrier can greatly increase the concentration of puerarin in tears, enhance the pre-ocular retention time than that of eye drops.

Preparation and evaluation of a contact lens vehicle for puerarin delivery.

The purpose of this study is to develop a soft contact lens vehicle for puerarin delivery to alleviate glaucoma. Poly(2-hydroxy-ethyl methacrylate-co-N-vinylpyrrolidone-co-methyl acrylate) (pHEMA-NVP-MA) contact lenses were prepared by UV irradiation of HEMA, NVP and MA, to which the cross-linker, a mixture of trimethylolpropane trimethacrylate (TMPTMA) and allyl methacrylate (AMA) (1:1, w/w) was added previously. The contact lenses were characterized by equilibrium swelling ratio (ESR) and tensile tester. The results showed that incorporation of poly-N-vinylpyrrolidone (PVP) component in the hydrogels caused increase of ESR and decrease of tensile strength. Co-polymerization of MA monomer in the hydrogel led to a slight drop of ESR and improved tensile strength of hydrogel. Four kinds of hydrated contact lenses with different PVP content were presoaked in PBS solution of puerarin and the in vitro drug release was measured. The contact lenses matrix incorporated with PVP had a remarkable loading capacity of puerarin. In rabbit eyes, the presoaked contact lenses extended the mean resident time of puerarin to 77.45 min from 12.88 min of 1% puerarin eye drops. Moreover, contact lens presoaked in puerarin solution at the concentration of 0.802 mg/ml showed about the same bioavailability (AUC(0-t)) in tear fluid as that of the puerarin eye drops. This kind of presoaked contact lens has potential application as vehicle of puerarin to alleviate glaucoma.

Cyclodextrin-containing hydrogels for contact lenses as a platform for drug incorporation and release.

Poly(2-hydroxyethyl methacrylate) hydrogels containing beta-cyclodextrin (pHEMA/beta-CD) have been investigated as a platform for sustained release of ophthalmic drugs. First of all, pHEMA/beta-CD hydrogel membranes and contact lenses were prepared by photopolymerization of HEMA, mono-methacrylated beta-CD (mono-MA-beta-CD) and trimethylolpropane trimethacrylate using a cast molding process. The hydrogels were characterized by Fourier transform infrared spectroscopy, equilibrium swelling ratio (ESR) and tensile tester. The results showed that the incorporation of beta-CD in the hydrogels increased the ESR and tensile strength. Then, puerarin was used as a model to evaluate drug loading and in vitro and in vivo release behavior of the pHEMA/beta-CD hydrogels. It was revealed that puerarin loading and in vitro release rate were dependent on beta-CD content in the pHEMA/beta-CD hydrogels. In rabbit eyes the pHEMA/beta-CD hydrogel contact lenses exhibited longer mean residence times (MRT(F)) of puerarin in tear fluid than that of pHEMA contact lenses and 1% puerarin eye drops. The puerarin concentration in the aqueous humor of rabbit reached a maximum of 0.81microg ml(-1) after wearing the pHEMA/beta-CD contact lens, which had been presoaked in 0.802mg ml(-1) puerarin solution for 4.81h. Also, the pHEMA/beta-CD contact lenses had a higher drug bioavailability in aqueous humor than puerarin eye drops. The data demonstrate that pHEMA/beta-CD hydrogel contact lenses can effectively deliver puerarin through the cornea.