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Objective: Aim of the present work was to optimize and formulate resveratrol loaded vesicular cream intended for dermal delivery of resveratrol with high skin deposition potential. Methods: Formulation was developed and optimized using Central Composite Design. Amount of phospholipid and sodium cholate were selected as critical material attributes and vesicle size and entrapment efficiency of resveratrol were taken as critical quality attributes. To increase the skin applicability and patient compliance, vesicles were further developed as vesicular cream which was then thoroughly characterized for physicochemical parameters, ex vivo skin permeation/deposition profile and antioxidant potential. Results: Vesicle size and entrapment efficiency of the optimized batch were found to be 178.9 ± 12.87 nm with 72.32 ± 3.45% respectively. Physicochemical properties and viscosity of cream formulation were also found to be favorable for skin applicability. Permeation flux at the end of 24 h was found to be 2.70 ± 0.73, 4.45 ± 0.56 and 4.95 ± 0.69 µg cm -2 h -1 for conventional cream, vesicular dispersion, and vesicular cream formulation respectively. Higher drug deposition in the skin via vesicular cream formulation was observed i.e. 335.2 ± 4.12 µg cm -2 (70.16 ± 0.87%) as compared to conventional cream i.e. 67.12 ± 19.63 µg cm -2 (14.05 ± 4.11%). Resveratrol encapsulated in vesicular cream has retained its inherent antioxidant activity suggesting the stability of resveratrol in vesicular cream. Conclusion: Thus, it can be concluded that deformable vesicular cream is capable of delivering encapsulated bioactive in deeper layers of skin, where it can be retained for achieving higher dermatological benefits.

Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD). Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release. Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved. Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area.

This study aimed to prepare and characterize organogels containing microparticles of ascorbic acid (AA) obtained from propolis by-product. The formulations F1 (5% of microparticles) and F2 (10% of microparticles) were evaluated regarding rheological and textural properties, antioxidant and radical scavenging activity, in vitro release and cellular studies. The organogels showed plastic flow behavior and rheopexy. The textural parameters were within acceptable values for semisolid formulations. The antioxidant capacity of organogels F1 and F2 by the DPPH assay demonstrated IC 50 ranging from 1523.59 to 1166.97 μg/mL, respectively. For the FRAP assay, the values found were 842.88 and 956.14 μmol of FSE/g formulation, respectively. Good scavenging activity against nitrogen species was observed. The concentration of 63 μg/mL did not present toxicity on HaCaT and HFF-1 cells. In vitro release profile of AA from organogels showed a slow pattern of drug release, mainly for F2. Therefore, the proposed organogel containing AA microparticles with propolis by-product matrix represents a promising platform for topical drug delivery with antioxidant effect.

Since FDA approval of the first transdermal patch in 1979, the utilizing of skin as a route of systemic drug administration has attracted the attention of the formulation scientists. The liposomes research in the area of transdermal drug delivery has been around for decades. This study aimed at comparing the latest gel-core liposomes (hyaluosomes) with nonconventional liposomal systems such as propylene glycol (PG)-liposomes, ethosomes, transferosomes and conventional liposomes loaded with ketoprofen. The modified thin-film hydration method was used to prepare these liposomal systems; size, zeta potential, EE%, TEM, rheological properties, in vitro release and ex vivo permeation studies were performed. Vesicle size and PDI ranged from 160 nm to 700 nm and 0.15 to 0.5, respectively. More interestingly, thermal gelation and shear-thinning characteristics were only recorded with hyaluosomes; while Newtonian behavior and low viscosity values (2 mPas.s to 6 mPa.s) were shown with all other liposomal systems. Hyaluosomes recorded superior (3-fold increases) transdermal permeation characteristics (flux and permeability coefficient), compared with other liposomal systems. With the advancement in liposomal sciences, this study warrants hyaluosomes as a promising transdermal liposomal system for favorable rheological characteristics as well as superior transdermal permeation that proved greater capacity than conventional and other non-conventional liposomal systems.

Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box-Behnken experimental design methodology. Drug (SL), gelling agent (F-127), and emulsifier (Propylene glycol, PG) were selected as independent variables, while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25 mg SL, 20 g F-127, and 1 g PG) and S14 (contain 50 mg SL, 18 g F-127 and 1 g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68 mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69-244.16 N/cm 2 ) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8 h. Permeation flux for the S10 gel was 0.0002 mg/min/cm 2 . Results demonstrated that the potential use of SL gels can enhance the therapeutic effect of SL through the intranasal administration.

Compression coating is a possible process for obtaining zero-order release. Nifedipine compression-coated (CC) di-matrix depot tablets were prepared from a single punch tablet press with low viscosity hydroxypropyl cellulose (HPC-L) as the inner polymer, and with middle viscosity hydroxypropyl cellulose (HPC-M), HPC-L and Eudragit RSPO as outer polymers. The release behavior and mechanisms in vitro of the final tablets were investigated, and gravimetric analysis was used to study the release mechanism. The fast release of the core depot and slow release of the outer depot with time formed total zero-order release. The results showed that the formulation presented ideal zero-order release at the weight ratio of nifedipine 3:5 (core: layer), the combination of HPC-L and HPC-M (56:25) in the outer depot, and with the core depot placed in the center. The CC tablets released to more than 95% in 24 h and fitted a zero-order model with the equation M t /M ∞  = 0.038t (R 2  = 0.98555). In conclusion, zero-order release of nifedipine over 24 h could be achieved by applying polymer HPC-L and HPC-M with the compression coating technique.

Periodontal disease is a chronic inflammation of gum and tissues that surround and support the teeth. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in the treatment of periodontitis to ease swelling and inflammation. One approach of treating periodontitis is loading the NSAIDs in local drug delivery systems. Therefore, the objective of this study was to investigate the local delivery of the NSAIDs model drug ibuprofen to treat periodontitis using different types of gel formulations (hydrogel, oleogel, and bigel). Gel formulations were characterized in terms of their rheological properties (flow behavior, viscoelastic, and bioadhesive properties) using a controlled-stress rheometer. The in vitro drug release of ibuprofen from gel formulations was investigated using Franz diffusion cells. Gels exhibited more solid-like (elastic) behavior. The viscosity and viscoelastic properties were in the order of oleogel > bigel > hydrogel, respectively. In bioadhesion study, mucin dispersion/plain ibuprofen-hydrogel mixture showed a frequency-dependent interaction of ΔG' = -31 and ΔG' = + 53 Pa at 1 and 10 rad/s, respectively. A strong positive interaction (ΔG' = + 6000 and +130,667 Pa at 1 and 10 rad/s, respectively) was found in mucin dispersion/plain ibuprofen-oleogel mixture. The extent of the negative interaction increased in mucin dispersion/plain ibuprofen-bigel mixture (ΔG' = -59,000 and -79,375 Pa at 1 and 10 rad/s, respectively). After 6 h, ibuprofen release from hydrogel, oleogel, and bigel was 59.5 ± 2.2, 80.6 ± 3.9, and 94.6 ± 3.2%, respectively. Results showed that the rheological and bioadhesive properties and in vitro drug release were influenced by the type of gel formulations.

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force - time curves revealed a direct relation of maximum disintegration force (F max ) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

Plasticizers play a crucial role in various process of microencapsulation. In this study, the effect of incorporation of plasticizer in process of emulsion solvent evaporation was investigated on properties of ethyl cellulose (EC) microcapsules containing propranolol hydrochloride. The effect of plasticizer type and concentration were investigated on characteristics of microcapsules prepared from different viscosity grades of EC. Product yield, encapsulation efficiency, mean particle size, shape, surface characteristics, solid state of drug, and drug release profiles were evaluated. Product yield and encapsulation efficiency were not dependent on plasticizer type and concentration. However, encapsulation efficiency decreased with increase in EC viscosity grade in the most of the cases. The mean particle size was in the range of 724-797 μm and was not dependent on plasticizer type. Microcapsules formed in the presence of PEG had a very smooth surface with few pores. XRD and DSC studies revealed a reduction of drug crystallinity after microencapsulation especially in presence of PEG. The results showed that the presence of TEC and DEP with different concentrations had no marked effect on drug release from microcapsules containing different viscosity grades of EC. This was not the case when PEG was used, and despite its water solubility it reduced the drug release rate noticeably. The reduction in the drug release in the presence of PEG was concentration-dependent. The use of PEG as a plasticizer in process of emulsion solvent evaporation highly improved the EC microcapsule structure and retarded the drug release rate and therefore is recommended.

Objective: To evaluate the compatibility of commercially available eye drop surface tension with the tear film physiological range and to characterize commonly used ophthalmic excipients in terms of their surface activity under eye-biorelevant conditions., Significance: There are a number of quality requirements for the eye drops (e.g. tonicity, pH, viscosity, refractive index) that needs to comply with the physiological parameters of the eye surface. However, the adjustment of surface tension properties of the eye drops to the normal range of surface tension at the air/tear fluid interface (40-46 mN/m) has received rather less attention thus far. Yet, the surface tension at the air/tear fluid interface is of vital importance for the normal function of the eye surface., Methods: The surface tension compatibility of the isotonic aqueous solutions of commonly used ophthalmic excipients as well as 18 approved eye drops with the tear fluid have been evaluated using surface tension method., Results: Each ophthalmic ingredient including the preservatives, solubilizing agents and thickening agents can influence the surface tension of the final formulation. In case of complex ophthalmic formulations one should also consider the possible interactions among excipients and consequent impact on overall surface activity. Out of 18 evaluated eye drops, three samples were within, 12 samples were below and three samples were above the physiological range of the tear fluid surface tension., Conclusions: Our results provide a rationale for clinical studies aiming to assess the correlation between the eye drops surface tension and the tear film (in)stability.

We recently reported an amelogenin-chitosan (CS-AMEL) hydrogel as a promising biomimetic material for future in situ human enamel regrowth. To further optimize the necessary conditions for clinical applicability of CS-AMEL hydrogel, herein we studied the effects of viscosity and supersaturation degree on the size and orientation of synthetic crystals by means of scanning electron microscopy (SEM) and X-ray diffraction (XRD). Raising the hydrogel viscosity by increasing chitosan concentration from 1% to 2% (w/v) improved the orientation of the crystals, while a higher supersaturation (σ(HAp) >10.06, [Ca(2+)] >5 mM) resulted in the formation of random crystals with larger sizes and irregular structures. We conclude that optimal conditions to produce organized enamel-like crystals in a CS-AMEL hydrogel are: 2% (w/v) chitosan, 2.5 mM calcium, and 1.5 mM phosphate (degree of supersaturation = 8.23) and 200 µg/ml of amelogenin.

Guaifenesin is widely used to alleviate symptoms of excessive mucus accumulation in the respiratory tract. However, its mechanism of action is poorly understood. The authors hypothesized that guaifenesin improves mucociliary clearance in humans by reducing mucin release, by decreasing mucus viscoelasticity, and by increasing mucociliary transport. To test these hypotheses, human differentiated airway epithelial cells, cultured at an air-liquid interface, were treated with clinically relevant concentrations of guaifenesin by addition to the basolateral medium. To evaluate the effect on mucin secretion, the authors used an anzyme-linked immunosorbent assay (ELISA) to measure the amounts of MUC5AC protein in apical surface fluid and cell lysates. To measure mucociliary transportability, additional cultures were treated for 1 or 6 hours with guaifenesin, and the movement of cell debris was measured from video data. Further, the authors measured mucus dynamic viscoelasticity using a micro cone and plate rheometer with nondestructive creep transformation. Guaifenesin suppressed mucin production in a dose-dependent manner at clinically relevant concentrations. The reduced mucin production was associated with increased mucociliary transport and decreased viscoelasticity of the mucus. Viability of the cultures was not significantly affected. These results suggest that guaifenesin could improve mucociliary clearance in humans by reducing the release and/or production of mucins, thereby altering mucus rheology.

This is the first study that evaluates the influence of the compartmental design of the micropump Aeroneb Go nebulizer and the viscosity of a proliposome hydration medium on vibrating-mesh aerosolization of liposomes. Ethanol-based proliposomes comprising soya phosphatidylcholine and cholesterol (1:1 mole ratio) were hydrated by using isotonic NaCl (0.9%) or sucrose (9.25%) solutions to generate liposomes that entrapped approximately 61% of the hydrophilic drug, salbutamol sulphate. Liposomes were aerosolized by the nebulizer to a two-stage impinger. For both formulations, the aerosol mass output was higher than the phospholipid output, indicating some accumulation of large liposomes or liposome aggregate within the nebulizer. Using NaCl (0.9%) solution as the dispersion medium, aerosol droplet size was much smaller and aerosol mass and phospholipid outputs were higher. This was attributed to the lower viscosity of the NaCl solution, resulting in a reduced retention of the aerosols in the "trap" of the nebulizer. For the entrapped salbutamol sulphate, although the "fine particle fraction" was relatively high (57.44%), size reduction of the liposomes during nebulization caused marked losses of the drug originally entrapped. Overall, liposomes generated from proliposomes when using this nebulizer showed high nebulization output and small droplet size. However, further work is required to reduce the losses of the originally entrapped drug from liposomes.

A formulation and process development study was performed to formulate recombinant human deoxyribonuclease I as a powder for inhalation. First, excipient compatibility (with bovine DNase as a model substance) was examined with a stability study at stressed conditions (60 and 85 degrees C) while monitoring for occurrence of the Maillard reaction. Next, powders for inhalation were prepared by spray drying and spray freeze drying. We found that spray drying with inulin as stabilizer resulted in the best powder for inhalation. Finally, an ex-vivo test with the spray dried rhDNase I/inulin powder significantly decreased elastic and viscous moduli of sputum from five cystic fibrosis patients.

Complexation between poly(methyl vinyl ether-maleic anhydride) copolymer (Gantrez AN 169) and polyvinylpyrrolidone (PVP K-90D) in aqueous solutions were investigated using a viscometric method and Raman spectroscopy. The composite films with different weight ratios of PVP to Gantrez were prepared in the presence of N-methyl-2-pyrrolidone. The release profiles of diclofenac sodium (DS) from these films were determined and the bioadhesive properties measured. An interpolymer complex was formed through hydrogen bonding between the carbonyl groups of PVP and the hydroxyl groups of Gantrez. The formation of interpolymer hydrogen bonds reduced the interaction of the polymers with water molecules, thus resulting in a lower solubility of the complex in water and a further retarded release of DS from the composite films. The interpolymer complexation was also found to increase the bioadhesive properties of the composite films to a silicone elastomer substrate. The complexation of PVP and the Gantrez copolymer in the composite films was a critical factor affecting the release of DS from the films and the bioadhesive properties of the films.

The objective of this investigation was to test the biodegradability of gellan gum in the presence of galactomannanase in order to explore its suitability for the development of colon-specific controlled delivery systems. Gellan beads containing azathioprine (AZA) were prepared by ionotropic gelation in the presence of Ca2+ ions and were coated with an enteric polymer, Eudragit S-100. The effects of the simulated colonic fluid (SCF, pH 7.4 phosphate buffer) containing 15 mg/mL of galactomannanase on the in vitro release profiles of uncoated and enteric-coated beads were investigated, and the morphological changes in the structure of uncoated beads were assessed by scanning electron microscopy (SEM). In addition, 1% solution of deacetylated gellan gum was prepared and several aliquots of the resulting solution were evaluated rheologically to determine the concentration- and time-dependent effects of galactomannanase. Based on the percent drug released at 2 h, approximately 10% greater amount of drug was released in the SCF containing galactomannanase when compared with the enzyme-free dissolution medium. Results of rheological studies demonstrated that effects of galactomannanase on the viscosity of gellan gum solution are concentration-dependent rather than time-dependent. A significant decrease in the viscosity was noted in the presence of galactomannanase at a concentration of 15 mg/ mL, indicating that the polysaccharide degraded in an enzymatic reaction. SEM micrographs showed a distinct disruption of the polymeric network in the SCF. Overall, the results suggest that gellan gum undergoes significant degradation in the presence of galactomannanase which in turn facilitates the drug release from beads in the SCF in a controlled manner, thus approving the suitability of gellan gum as a carrier for controlled colonic delivery.

The aim of this study was to investigate isotropic mono- and diglyceride-based (MCMDG) systems, which are potential vehicles for injectable products containing both hydrophilic and lipophilic drugs. For two-component systems, MCMDG was mixed with various masses of water. For three-component systems, the samples were prepared by mixing propylene glycol or glycerol formal or short-chain alcohols with MCMDG prior to the addition of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. Solubilities of levamisole phosphate (hydrophilic) and abamectin (lipophilic) were determined in the isotropic formulations using high-performance liquid chromatography assay. The isotropic region in the two-component systems had a water content of up to 18% at 25 degrees C. Solvents such as propylene glycol (PG), glycerol formal (FG), and ethyl alcohol increased the isotropic region. The area of isotropic region in these three-component systems increased with increasing temperature. The area of the isotropic region became larger with decreasing dielectric constant and solubility parameter of the series of short-chain alcohols, except n-butyl alcohol, at 25 degrees C. The systems exhibited Newtonian behavior. The solubility of both hydrophilic and lipophilic drugs was high in formulations at 25 degrees C. It was concluded that more water was solubilized in MCMDG/short-chain alcohols/water systems, and the isotropic region in the short-chain alcohol systems enlarged compared with MCMDG/PG/water or MCMDG/GF/water systems, except the n-butyl alcohol system. Hydrophilic and lipophilic drugs solubilize in the systems. The isotropic formulations containing MCMDG may represent an alternative to more traditional formulations for injectable formulations containing both lipophilic and hydrophilic drugs.

Three groups of male Wistar rats received daily subcutaneous injections of 10 mg/kg of hydrocortisone (HC group), 300 mg/kg of beta-aminopropionitrile (BAPN group), or saline (control group), for 10 days. The shear stress-strain and stress-relaxation properties of the incisor periodontal ligament were examined in transverse sections from dissected mandibles. Both the maximum shear stress and failure strain energy density increased significantly following the administration of hydrocortisone. The maximum shear stress decreased following the administration of BAPN. However, the stress-relaxations in the initial 10 min did not show significant differences among the three groups. Polarized light microscopic analysis revealed that the retardation value of the collagen fibers was highest in the HC group and lowest in the BAPN group for the bone-related area, but not for the tooth-related and middle areas of the ligament. It is suggested that the changes induced by hydrocortisone or BAPN occurred mainly in the elastic components and to a minor extent in the viscous components although the physical and biomechanical properties are determined by the interaction of all the various components. We also suggest that the main response to the drugs occurred in the collagen fibers in the bone-related area of the ligament.

The inflammatory reaction in the human gastric mucosa to Helicobacter pylori could be initially triggered by an array of cytokines expressed in infected gastric epithelial cells. The spiral morphology and flagella of these organisms could increase their velocity in a viscous environment such as methylcellulose solution. The goal of this study was to determine whether modification of H. pylori motility could influence the expression of cytokine genes from gastric epithelial cells infected with H. pylori. Adherent human gastric epithelial cells were cultured and overlaid with methylcellulose solutions of varying viscosity. These epithelial cell layers covered with methylcellulose solution were inoculated with H. pylori. RNAs were then extracted from the gastric epithelial cells. Various cytokine gene expressions were assessed and quantified by reverse transcription-polymerase chain reaction (RT-PCR) and standard synthetic RNA. Cytokine proteins were also measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA for interleukin(IL)-8 was upregulated in H. pylori-infected gastric epithelial cells overlaid with methylcellulose of 15 centipoise (cp) viscosity. The expression of mRNA for IL-1 alpha, IL-8, monocyte chemotactic protein (MCP)-1 and granulocyte macrophage colony-stimulating factor (GM-CSF) was also upregulated in H. pylori-infected gastric epithelial cells overlaid with methylcellulose solution of the same viscosity. The number of molecules of the expressed cytokine transcripts also paralleled the amounts of protein secreted from gastric epithelial cells infected with H. pylori. These results suggest that methylcellulose solution (simulating the mucus layer in vivo) could increase contact of H. pylori with gastric epithelial cells by increasing its motility. This could result in the upregulation of mRNA for proinflammatory cytokines in gastric epithelial cells, therefore enhancing inflammatory reaction at H. pylori-infected sites.

The changes in the structure and properties of erythrocyte membranes that are induced by free fatty acids and their derivatives have been studied. The state of the membrane has been evaluated using the activity of membrane-bound acetylcholinesterase (AChE), the pyrene monomer/excimer fluorescence intensity ratio as an indicator of membrane lipid microviscosity and the fluorescence of membrane-bound 1-anilinonaphtalene-8-sulphonic acid (ANS). Free fatty acids and corresponding aliphatic aldehydes induced an inhibition of membrane-bound AChE, effectively decreased the bulk lipid and protein-bound lipid microviscosity, and quenched the fluorescence of membrane-bound ANS. The type and efficiency of the enzyme inhibition, as well as the efficiency of microviscosity decrease and ANS fluorescence quenching, depended on the hydrophobicity and the end group in the effector molecule. Therefore, it is proposed that fatty acids and related compounds perturb the lipid bilayer and disturb the protein-lipid complementarity of the human erythrocyte membrane.

Normal tendons, normal palmar aponeuroses and specimens from patients with Dupuytren's disease, namely apparently normal palmar aponeuroses and contracture bands were subjected to elastase and chondroitinase ABC digestion. Maximum Young's modulus, normalized hysteresis loop and residual elongation were determined before and after enzyme treatment. In normal tendons, normal and apparently normal palmar aponeuroses both normalized hysteresis loop and residual elongation increased significantly after elastase treatment, whereas the stiffness decreased. Normalized hysteresis loop and residual elongation display changes corresponding to the amount of digested elastin. The increased viscosity of untreated contracture bands containing less elastin, as compared to normal palmar aponeurosis, was not affected by elastase. Obviously, the elastic fibers in normal shape and distribution are responsible for maintaining an elastic status with a low viscous stress component. With the exception of contracture bands chondroitinase ABC caused a minor increase of residual elongation and as opposed to elastase a decrease of normalized hysteresis loop indicating an increased mobility of the tissue fibers.