Search

Dissolving microneedles (MN) containing cyclosporin A (CyA) were prepared for local delivery of CyA into the dermal layer. The efficacy of using MN to deliver CyA, an insoluble and high molecular weight drug, was observed and compared with oral administration of solubilized CyA. Microneedles containing CyA (CyA MN) were prepared using a closed, low-temperature molding process. The mechanical properties of CyA MN and phase separation were studied regarding the content of CyA. CyA MN were inserted into porcine skin for a predetermined time, and the dissolution and delivered amount of CyA were measured in vitro with an optical microscope and high-performance liquid chromatography (HPLC) analysis of the extracted CyA. A pharmacokinetic study of CyA MN was performed in vivo by administering 10% CyA MN, and the pharmacokinetic profile was compared with that of orally administered CyA. Pyramidal CyA MN (600 μm long, 250 μm wide) were prepared. CyA MN penetrated skin successfully with up to 50% CyA content. When 10% CyA MN were pressed into porcine skin for 60 min, 65% of MN length was dissolved and 34 ± 6.5 μg of CyA in MN was delivered into the skin. Under the same conditions with 10% CyA MN administered to rats, CyA MN showed Tmax of 8 h, Cmax of 15.9 ng/ml, and area under curve (AUC) of 686, compared to Tmax of 2 h, Cmax of 18.205 ng/ml, and AUC of 254 for oral administration of solubilized CyA. A therapeutic dose of CyA for treatment of psoriasis was delivered via MN into the skin layer without solubilization of CyA. Due to the hydrophobic properties and high molecular weight of CyA, the safety of CyA delivery was improved using dissolving microneedles because the slow systemic absorption and local treatment enabled CyA to remain in the skin for a longer time. Microneedles are an effective method with high bioavailability for local dermal delivery of insoluble drugs.

Objectives: The purpose of this study was to evaluate a partially purified extract (elm extract) from the Ulmi cortex (Ulmi macrocarpa Hance) and its active ingredient, a mix of procyanidin oligomers (3 to 12 flavan-3-ol monomers, an average molecular weight of 1,518 with an average polymerization degree of 5.3) for a possible inhibitory effect against proteases. Background: Host-derived matrix metalloproteinases (MMPs) and bacterial proteases play important roles in the gingival tissue destruction that is a characteristic of periodontitis. The inhibitors of these proteases may be developed into therapeutic agents against periodontitis. Methods: The inhibitory effects were assessed by gelatin zymography. The MMPs tested were originated from the gingival crevicular fluid (GCF) of adult periodontitis patients and from the conditioned media of cultured periodontal ligament (PDL) cells, which provided the proMMP-2 and activated MMP-2 when treated with a periodontopathogen, Treponema lecithinolyticum. Bacterial enzymes tested were secreted forms from two major periodontopathogens, Porphyromonas gingivalis and Treponema denticola. In addition, the inhibitory effects on trypsin-like enzymes from these two periodontopathogens were assayed by the n-benzoyl-DL-arginine-naphthylamide (BANA) test. Results: The elm extract and the procyanidin oligomer (100-1,000 μg/ml) exhibited potent inhibitory effects on the MMPs in GCF (chiefly MMP-8 and MMP-9), the pro and active forms of MMP-2, and secreted and trypsin-like enzymes from T. denticola and P. gingivalis. Conclusions: These results suggest that elm cortex should be considered as a potential agent against periodontal diseases, due to its inhibitory action on MMPs and the proteases of periodontopathogens.