Surface Force Measurements of Mussel-Inspired Pressure-Sensitive Adhesives.

Translating fundamental studies of marine mussel adhesion into practical mussel-inspired wet adhesives remains an important technological challenge. To adhere, mussels secrete adhesive proteins rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (Dopa) and positively charged lysine. Consequently, numerous synthetic adhesives incorporating catecholic and cationic functionalities have been designed. However, despite widespread research, uncertainties remain about the optimal design of synthetic mussel-inspired adhesives. Here, we present a study of the adhesion of mussel-inspired pressure-sensitive adhesives. We explore the effects of catechol content, molecular architecture, and solvent quality on pressure-sensitive adhesive (PSA) adhesion and cohesion measured in a surface forces apparatus. Our findings demonstrate that the influence of catechol content depends on the choice of solvent and that adhesive performance is dictated by film composition rather than molecular architecture. Our results also highlight the importance of electrostatic and hydrophobic interactions for adhesion and cohesion in aqueous environments. Together, our findings contribute to an improved understanding of the interplay between materials chemistry, environmental conditions, and adhesive performance to facilitate the design of bioinspired wet adhesives.

Synergic adhesive chemistry-based fabrication of BMP-2 immobilized silk fibroin hydrogel functionalized with hybrid nanomaterial to augment osteogenic differentiation of rBMSCs for bone defect repair.

Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms. In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the Bm@nHG-SFD hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies.

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems.

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.

Mussel-inspired adhesive and polypeptide-based antibacterial thermo-sensitive hydroxybutyl chitosan hydrogel as BMSCs 3D culture matrix for wound healing.

Hydrogels have gained great attentions as wound dressing. Binding to the tissue and preventing wound infection were the basic requirements for an "ideal dressing". We employed l-DOPA and ε-Poly-l-lysine to modify thermo-sensitive hydroxybutyl chitosan (HBC) to obtain (l-DOPA) - (ε-Poly-l-lysine)-HBC hydrogels (eLHBC). The eLHBC exhibited an almost 1.5 fold (P < 0.01) increase in wet adhesion strength compared to HBC. Upon the introduction of ε-Poly-l-lysine, eLHBC presented inherent antimicrobial property and prevented wound infection and inflammation response. Bone marrow mesenchymal stem cells (BMSCs) encapsulated in the eLHBC (BMSCs ⊂ eLHBC) could secret cytokins and growth factors via paracrine and promote the migration of fibroblast cells. BMSCs ⊂ eLHBC enhanced the complete skin-thickness wound healing via promoting collagen deposition and inhibiting infection and inflammation in vivo with wound closure rate being above 99 % after 15 days. The bioinspired, tissue-adhesive eLHBC could serve as advanced wound dressings for facilitating tissue repair and regeneration.

Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces.

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

An anti-infective hydrogel adhesive with non-swelling and robust mechanical properties for sutureless wound closure.

A non-swelling hydrogel adhesive is urgently needed in clinical application for wound closure; however, preparing a non-swelling hydrogel adhesive with superior mechanical and tissue adhesion properties remains a challenge. In this study, we developed a new family of non-swelling hydrogel adhesives composed of Pluronic F127 diacrylate, poly(ethylene glycol) diacrylate, modified sodium alginate, and tannic acid. Physical and biological properties of the hydrogels were systematically evaluated in vitro/vivo. The results indicated that the hydrogels exhibited non-swelling features, robust mechanical properties and good adhesion abilities toward various tissues. The hydrogels also exhibited good cytocompatibility and strong antibacterial activities against S. aureus and E. coli. Additionally, the hydrogel could be used for sutureless wound closure and displayed better advantages compared to sutures and commercial adhesive pads. The above results demonstrated that our non-swelling hydrogel adhesive with robust mechanical properties holds great promise for applications in clinical surgery.

Multifunctional composite hydrogel bolus with combined self-healing, antibacterial and adhesive functions for radiotherapy.

Radiotherapy is a commonly used method for curing cancers that appear on or just below the skin. Because of the dose build-up effect of X-rays, boluses made of various materials such as silica and wax are clinically applied on patients to increase the skin dose for an enhanced therapeutic effect. However, these commercial boluses can't conform well to the skin's surface with some curvature, resulting in radiation dose attenuation/loss at the lesion location. To address this limitation, we have developed a nano-titanium dioxide (nTiO2)-incorporated polyurethane/polyacrylamide (TPU/PAAm) hydrogel with multi-functions for fabricating a desirable bolus. The obtained hydrogel exhibits excellent mechanical, adhesive and self-healing properties and can fit closely to the surface of patients with any 3D curvature, eliminating the air gap which is a common problem for commercial boluses applied on patients. In particular, it is encouraging that when using the bolus made of TPU/PAAm hydrogel, the dose distribution including dose coverage, conformability and homogeneity within the planning target volume (PTV) is far superior to that when using the commercial bolus. A sufficient dose shifts toward the surface of the head model and is located only in the lesion site, demonstrating that TPU-PAAm hydrogel can provide an optimal dose distribution and be clinically effective for treating superficial tumors. Furthermore, nTiO2 particles feature uniform dispersion at the nanometer level in hydrogel after being modified by 2,2-bis(hydroxymethyl)propionic acid (DMPA) based on coordination chemistry, endowing the hydrogel with long-acting antibacterial ability. The good cell affinity of TPU-PAAm hydrogel is also confirmed in this study, further ensuring that the TPU-PAAm hydrogel prepared here is a desirable candidate as a tissue equivalent with the advantages of convenient use and effectiveness in radiotherapy.

Mussel-Inspired Polymerization of Peptides: The Chemical Activation Route as Key to Broaden the Sequential Space of Artificial Mussel-Glue Proteins.

A previously introduced tyrosinase-activated polymerization of Tyr- and Cys-bearing peptides yielding artificial mussel-glue proteins is realized without the need of the specific enzyme by a chemical activation route. This decouples the sequence of polymerizable peptides (unimers) from the constraints of tyrosinase substrates and enables the polymerization of minimal motifs such as Dopa-Lys-Cys (Umini *KC ) or Dopa-Gly-Cys (Umini *GC ). In the polymerization procedure, sodium periodate is used to oxidize Dopa residues of the unimers to Dopa-quinones to which the thiol of a Cys residue is added in a Michael-type reaction. The resulting polyUmini *KC and polyUmini *GC exhibit a thiol-catechol connectivity as a potent adhesive functionality at each repeat unit. QCM-D experiments show the excellent substrate adsorption properties of the products from the chemically activated polymerization. On aluminum oxide surfaces, polyUmini *KC rapidly forms a coating, even under seawater model conditions and the coating resists rinsing with hypersaline solution of 4.2 M salt mixtures. While the sodium periodate oxidation is less specific than the tyrosinase reaction and requires the implementation of Dopa instead of Tyr residues into the polymerizable unimers, the chemical route makes scale-up more easily accessible.

Enhanced Adhesion and Cohesion of Bioinspired Dry/Wet Pressure-Sensitive Adhesives.

The byssus-mediated adhesion of marine mussels is a widely mimicked system for robust adhesion in both dry and wet conditions. Mussel holdfasts are fabricated from proteins that contain a significant amount of the unique catecholic amino acid dihydroxyphenylalanine, which plays a key role in enhancing interfacial adhesion to organic and inorganic marine surfaces and contributes to cohesive strength of the holdfast. In this work, pressure-sensitive adhesives (PSAs) were synthesized by copolymerization of dopamine methacrylamide (DMA) with common PSA monomers, butyl acrylate and acrylic acid, with careful attention paid to the effects of catechol on adhesive and cohesive properties. A combination of microscopic and macroscopic adhesion assays was used to study the effect of catechol on adhesion performance of acrylic PSAs. Addition of only 5% DMA to a conventional PSA copolymer containing butyl acrylate and acrylic acid resulted in 6-fold and 2.5-fold increases in work required to separate the PSA from silica and polystyrene, respectively, and a large increase in 180° peel adhesion against stainless steel after 24 h storage in both ambient and underwater conditions. Moreover, the holding power of the catechol PSAs on both steel and high-density polyethylene under shear load continuously increased as a function of catechol concentration, up to a maximum of 10% DMA. We also observed stark increases in shear and peel adhesion for the catecholic adhesives over PSAs with noncatecholic aromatic motifs, further underlining the benefits of catechols in PSAs. Overall, catechol PSAs perform extremely well on polar and metallic surfaces. The advantage of incorporating catechols in PSA formulations, however, is less straightforward for peel adhesion in nonpolar, organic substrates and tackiness of the PSAs.

Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia.

BACKGROUND: Xerostomia is caused by different factors such as side effects of medication, radiotherapy by head and neck cancer as well as Sjögren syndrome. AIM: The goal was to synthesize novel preactivated chitosan conjugates and to design adhesive dosage forms comprising sialagogue pilocarpine. METHODS: Unmodified chitosan (CH) was covalently linked to sulfhydryl possessing mercaptonicotinic acid (MNA) via amide bond formation. In a second step, preactivation occurred via disulfide bond establishment between sulfhydryl linked chitosan and preactivation ligand MNA. Mucoadhesive and mucoprotective properties were scrutinized on buccal mucosa. Safety assessment was performed on head and neck squamous cells. Histology assay was conducted on buccal tissue. Pilocarpine was scrutinized in terms of controlled release behavior. RESULTS: Novel preactivated CH was successfully synthesized and considered as not harmful to the cells at all. Furthermore, mucoadhesion was 1.3-fold improved in the presence of preactivated chitosan as compared to respective unmodified one. Pilocarpine exhibited a 3.1-fold controlled release in presence of novel synthesized chitosan as in comparison to unmodified CH. CONCLUSION: The novelty of this promising polymeric carrier lies in the synthesis procedure leading to a pronounced mucoadhesive, mucoprotecting and controlled release encouraging dosage form in the management of xerostomia.

Biomimetic chitosan-graft-polypeptides for improved adhesion in tissue and metal.

Inspired by the mussel foot protein and chitosan-based macromolecular adhesives, a series of chitosan-graft-polypeptides were synthesized by ring-opening polymerization of three N-carboxyanhydrides (NCAs) - 3,4-dihydroxyphenylalanine-N-carboxyanhydride (DOPA-NCA), cysteine-NCA (Cys-NCA) and arginine-NCA (Arg-NCA) - using partial-NH2-protected chitosan as an initiator. These copolymers demonstrated good biodegradability and low cytotoxicity. The results of lap-shear adhesion test showed that the maximum lap-shear adhesion strength on the porcine skin and aluminum sheet were 195.97 ± 21.1 kPa and 3080 ± 320 kPa, respectively, and the maximum tensile adhesion strength on bone was 642.70 ± 61.1 kPa. The rat experiment in vivo showed that these copolymers exhibited good hemostatic performance and can promote the healing of skin wound and bone fracture. It is expected that thesecopolymeric adhesives will have broad applications in hemostasis and soft tissue adhesions.

Mechanical characterization and ex vivo evaluation of anticancer and antiviral drug printed bioadhesive film for the treatment of cervical cancer.

As research progresses on personalized medicines, it is clear that personalized and flexible formulations can provide effective treatment with reduced side effects especially for diseases like cancer, characteristic of high patient variability. 2D and 3D printers are frequently reported in the literature for the preparation of pharmaceutical products with adjusted dose and selected drug combinations. However, in-depth characterization studies of these formulations are rather limited. In this paper, ex vivo and mechanical characterization studies of antiviral and anticancer drug printed film formulations designed for personalized application were performed. Effects of the printing process with pharmaceutical formulations such as paclitaxel (PCX):cyclodextrin (CD) complex or cidofovir (CDV) encapsulated into poly(ethylene glycol)-polycaprolactone (PEG-PCL) nanoparticles on the films were evaluated through a series of mechanical characterization studies. Inkjet printing process was found to cause no significant change in the thicknesses of the film formulations, while mechanical strength and surface free energy increased and nano-sized voids in the film structure decreased. According to the mechanical characterization data, the unprinted film had maximum force (Fmax) value of 15.6 MPa whereas Fmax increased to 43.8 MPa for PCX:CD complex printed film and to 37.7 MPa for the antiviral CDV-PEG-PCL nanoparticle printed film. In the light of ex vivo findings of sheep cervix-uterine tissue, bioadhesive properties of film formulations significantly improved after inkjet printing with different drug formulations. It has also been shown that the anticancer formulation printed on the film was maintained at the cervix tissue surface for >12 h. This study has shown for the first time that inkjet printing process does not adversely affect the mechanical properties of the bioadhesive film formulations. It has also been shown that durable bioadhesive film formulations for personalized dosing can be prepared by combining nanotechnology and inkjet printing.

Preparation and characterization of resorcinol-dialdehyde starch-formaldehyde copolycondensation resin adhesive.

A resorcinol-dialdehyde starch-formaldehyde (RDSF) copolycondensation resin adhesive was prepared by substituting high reactive dialdehyde starch for a portion of formaldehyde in the formulation. Fourier transforms infrared spectrometer (FTIR) analysis results confirmed that the copolycondensation reaction of the dialdehyde starch with resorcinol and formaldehyde was successful. The curing property, thermal stability, permeability and crystal structure of the RDSF adhesive were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscope (SEM), X-ray diffraction (XRD). The solids content, viscosity, curing time, bonding strength were also obtained. The results showed that the RDSF adhesive had a higher solids content, moderate viscosity, shorter curing time and better bond strength than a standard resorcinol-starch-formaldehyde (RSF) adhesive. It was found that dialdehyde starch could accelerate the curing rate, while decreasing the curing temperature and heat release during the curing process of RDSF. The dense cross-linked structure of the dialdehyde starch and resorcinol-formaldehyde (RF) system produced improved thermal stability. SEM results showed that the RDSF adhesive formed a thin and continuous adhesive layer on the surface of a poplar board, and filled the pores of the wood, which improved the bond strength. The crystal structure of the RDSF was not altered by addition of the starch, and the physicochemical properties of the adhesive were similar to those of a normal resorcinol-formaldehyde resin.

The Effect of Enzymolysis on Performance of Soy Protein-Based Adhesive.

In this study, bromelain was used to break soy protein molecules into polypeptide chains, and triglycidylamine (TGA) was added to develop a bio-adhesive. The viscosity, residual rate, functional groups, thermal behavior, and fracture surface of different adhesives were measured. A three-ply plywood was fabricated and evaluated. The results showed that using 0.1 wt% bromelain improved the soy protein isolate (SPI) content of the adhesive from 12 wt% to 18 wt%, with viscosity remaining constant, but reduced the residual rate by 9.6% and the wet shear strength of the resultant plywood by 69.8%. After the addition of 9 wt% TGA, the residual rate of the SPI/bromelain/TGA adhesive improved by 13.7%, and the wet shear strength of the resultant plywood increased by 681.3% relative to that of the SPI/bromelain adhesive. The wet shear strength was 30.2% higher than that of the SPI/TGA adhesive, which was attributed to the breakage of protein molecules into polypeptide chains. This occurrence led to (1) the formation of more interlocks with the wood surface during the curing process of the adhesive and (2) the exposure and reaction of more hydrophilic groups with TGA to produce a denser cross-linked network in the adhesive. This denser network exhibited enhanced thermal stability and created a ductile fracture surface after the enzymatic hydrolysis process.

Supramolecular Copolymerization of Short Peptides and Polyoxometalates: toward the Fabrication of Underwater Adhesives.

Peptide assembly has reached exquisite levels of efficiency in the creation of bioactive materials. However, we have not yet been able to take what we have learned from peptide assembly to develop a general strategy for the fabrication of biomimetic underwater adhesives, which retain significant advantages as medical glue for clinical treatment. Herein we report a simple approach to prepare peptide-based adhesives through the supramolecular polymerization of cationic peptides drove by polyoxometalates (PMs). Mass spectra, Fourier-transform infrared spectra and 183W NMR spectra confirmed the structural integrity of peptides and PMs during the coassembly process. Scanning electron microscopy demonstrated that the multivalent interactions between peptides and polyoxometaltes led to the formation of robust 3D network structures. The rheological study revealed that the peptide/PM assemblies exhibited mechanically rigid gel-like behavior and self-healing property. Interestingly, the assemblies showed the capacity to adhere various wet solid materials under waterline. The shear strength of the peptide-based adhesives are stronger than that of the commercially available fibrin glue. This finding is exciting and serves to expand our capability of the fabrication of peptide-based materials.

Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation. Furthermore, the influence of preactivated polymers on ciliary beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results showed, that 252.52±20.54µmol of the ligand was attached per gram polymer. No free thiol groups could be detected on the polymeric backbone indicating entire preactivation. Rheological investigations of polymer mucus mixtures revealed a 1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan-Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan). Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H2O2 as an oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity, indicating high stability towards oxidation. Addition of CaCl2 to Xan-Cys-MNA solutions caused a decrease in viscosity at nevertheless higher total viscosity. Results from CBF studies proved nasal safety for the novel conjugate. According to these results, entirely preactivated thiolated xanthan gum seems to be a promising excipient for nasal dosage forms in order to improve drug bioavailability.

Comparative studies of adhesion peptides based on l- or d-amino acids.

Detailed studies comparing solid-supported l- or d-amino acid adhesion peptides based on the sequence KLHRIRA were performed. Stability towards proteases and levels of cellular adhesion to the otherwise inert surface of PEGA resin were compared by using fluorescently labelled peptides. A clear difference in the peptide stability towards cleavage by subtilisin, trypsin, or papain was observed. However, all of the on-bead peptides provided an optimal surface for cell adhesion and proliferation. In long-term experiments, these properties were still found to be similar on the resins modified either with l- or with d-amino acids and unaffected by the nature of their fluorescence labelling at either terminus. These results support that the more accessible l-amino acids can be utilized for cell adhesion experiments and confirm the nonspecific interaction mechanism of cell binding to these peptides on the bead surface. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Hydrophobized plant polyphenols: self-assembly and promising antibacterial, adhesive, and anticorrosion coatings.

Hydrophobized plant polyphenols can be easily prepared by rational and controlled etherification of highly abundant aromatic hydroxyls with linear alkyl chains. The resultant organo-soluble polyphenols spontaneously formed fibrous structures and unravelled to be potential adhesive, anticorrosion, and antibacterial coatings.

Synthesis and characterization of thiolated ß-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery.

The objective of the present study was to synthesize and characterize cysteamine conjugated ß-cyclodextrin (ß-CD-Cys) as a novel mucoadhesive oligomeric excipient for intra-oral drug delivery. ß-CD-Cys conjugates were obtained in a two-step synthetic pathway, whereby, vicinal diol groups of the oligomer were oxidized using increasing concentrations of sodium-per-iodate (NaIO4), prior to the covalent coupling of cysteamine via reductive amination. Quantification of immobilized thiol groups through Ellman's test revealed 561.56 ± 81 µmol/g, 1054.26 ± 131 µmol/g and 1783.92 ± 201 µmol/g of free thiol groups attached to the oligomer backbone depending on the extent of oxidation. ß-CD-Cys conjugates at concentrations of 0.5% (m/v) showed no toxic effects on Caco-2 cells within 72 h. Furthermore, ß-CD-Cys conjugates displayed a 4-fold improved water solubility compared to the parent oligomer. ß-CD-Cys conjugates (ß-CD-Cys561, ß-CD-Cys1054 and ß-CD-Cys1783) showed 2.86-, 15.09- and 49.08-fold improved retention time on porcine intestinal mucosa and 9.66-, 16.43- and 34.51-fold improved on the porcine buccal mucosa, respectively. Formation of inclusion complexes of miconazole nitrate and ß-CD-Cys1054 resulted in 150-fold increased solubility of miconazole nitrate. According to these results, it seems that ß-CD-Cys conjugates might provide a new promising tool for delivery of poorly water soluble therapeutic agents, such as miconazole nitrate for intra-oral delivery.

Hydrothermal degradation of lignin: products analysis for phenol formaldehyde adhesive synthesis.

Corncob lignin was treated with pressurized hot water in a cylindrical autoclave in current investigation. With the aim of investigating the effect of reaction temperature and retention time on the distribution of degradation products, the products were divided into five fractions including gas, volatile organic compounds, water-soluble oil, heavy oil, and solid residue. It was found that hydrothermal degradation of corncob lignin in pressurized hot water produced a large amount of phenolic compounds with lower molecular weight than the raw lignin. Some phenolic and benzene derivatives monomers such as vanillin, 2-methoxy-phenol, 2-ethyl-phenol, p-xylene, and 1, 3-dimethyl-benzene were also identified in the degradation products. The products were further analyzed by GC-MS, GPC, 2D-HSQC, and (31)P-NMR to investigate their suitability for partial incorporation into phenol formaldehyde adhesive as a substitution of phenol. The results indicated that the reaction temperature had more effect on the products distribution than the retention time. The optimal condition for heavy oil production appeared at 290 °C with retention time 0 min. The compounds of heavy oil had more active sites than the raw lignin, suggesting that the heavy oil obtained from hydrothermal degradation of lignin is a promising material for phenol formaldehyde adhesive synthesis.