Fifty-kDa Hyaluronic Acid Upregulates Some Epidermal Genes without Changing TNF-α Expression in Reconstituted Epidermis

Background: Due to its strong water binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. However, based on its varying molecular size, skin penetration of HA may be limited. Recent studies have demonstrated that low-molecular-weight HA (LMW HA) may show a certain proinflammatory activity. We thus aimed to characterize an LMW-sized HA molecule that combines strong anti-aging abilities with efficient skin penetration but lacks potential proinflammatory effects. Methods: Total RNA and total protein were isolated from reconstituted human epidermis following incubation with HAs of various molecular weights (20, 50, 130, 300, 800 and 1,500 kDa). Tumor necrosis factor-alpha expression was determined using quantitative PCR. Genonnic and proteomic expression of various junctional proteins was determined using Affymetrix and common Western blotting techniques. Results: LMW HA of approximately 50 kDa did not significantly alter tumor necrosis factor-alpha expression compared to 20-kDa HA, but revealed significantly higher skin penetration rates than larger sized HA associated with increased expression of genes and proteins known to be involved in tight junction formation and keratinocyte cohesion. Conclusion: LMW HA of approximately 50 kDa shows better penetration abilities than larger-sized HA. In addition, LMW HA influences the expression of various genes including those contributing to keratinocyte differentiation and formation of intercellular tight junction complexes without showing proinflammatory activity. These observations contribute to current knowledge on the effects of LMW HA on keratinocyte biology and cutaneous physiology. Copyright (C) 2011 S. Karger AG, Base

Kitozanski umetci za periodontitis: Utjecaj količine lijeka, plastifikatora i umrežavanja na oslobađanje metronidazola in vitro

Chitosan based metronidazole (MZ) inserts were fabricated by the casting method and characterized with respect to mass and thickness uniformity, metronidazole loading and in vitro metronidazole release kinetics. The fabricated inserts exhibited satisfactory physical characteristics. The mass of inserts was in the range of 5.63 ± 0.42 to 6.04 ± 0.89 mg. The thickness ranged from 0.46 ± 0.06 to 0.49 ± 0.08 mm. Metronidazole loading was in the range of 0.98 ± 0.09 to 1.07 ± 0.07 mg except for batch CM3 with MZ loading of 2.01 ± 0.08 mg. The inserts exhibited an initial burst release at the end of 24 h, irrespective of the drug to polymer ratio, plasticizer content or cross-linking. However, further drug release was sustained over the next 6 days. Cross-linking with 10% (m/m) of glutaraldehyde inhibited the burst release by ~30% and increased the mean dissolution time (MDT) from 0.67 to 8.59 days. The decrease in drug release was a result of reduced permeability of chitosan due to cross-linking.Umetci metronidazola na bazi kitozana napravljeni su kasting metodom. Proučavana je ujednačenost mase i debljine, količina ljekovite tvari i kinetika oslobađanja metronidazola in vitro. Fizičke karakteristike umetaka bile su zadovoljavajuće: masa je bila u rasponu 5,63 ± 0,42 – 6,04 ± 0,89 mg, debljina od 0.46 ± 0.06 – 0.49 ± 0.08 mm with, količina metronidazola od 0,98 ± 0,09 – 1,07 ± 0,07 mg. Nakon 24 h iz svih umetaka, neovisno o omjeru ljekovite tvari i polimera, količini plastifikatora ili umrežavanju, dio metronidazola se naglo oslobodio. Međutim, daljnje oslobađanje je bilo polagano tijekom 6 dana. Umrežavanje s 10% (m/m) otopinom glutaraldehida spriječilo je naglo oslobađanje za ~30% i povećalo je srednje vrijeme oslobađanja (MDT) s 0,67 na 8,59 dana. Smanjenje u oslobađanju ljekovite tvari posljedica je smanjenja permeabilnosti umreženog kitozana

Therapeutic applications of viscous and injectable poly(ortho esters).

Poly(ortho esters) (POE) are hydrophobic and bioerodible polymers that have been investigated for pharmaceutical use since the early 1970s. Among the four described generations of POE, the third (POE III) and fourth (POE IV) are promising viscous and injectable materials which have been investigated in numerous biomedical applications. POE III has been extensively studied for ophthalmic drug delivery, it presents an excellent biocompatibility and is currently being investigated as a vehicle for sustained drug delivery to treat diseases of the posterior segment of the eye. POE IV is distinguishable by a highly reproducible and controlled synthesis, a higher hydrophobicity, and an excellent biocompatibility. It is currently under development for a variety of applications, such as ocular delivery, periodontal disease treatment and applications in veterinary medicine. This review will also focus on new perspectives for this promising family of polymers, such as guided tissue regeneration, treatment of osteoarthritis, as well as peptide and protein delivery

Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases

The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(ε-caprolactone) (CH/PCL) films and chitosan films were prepared. thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1∶0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1∶1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1∶0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 μg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained