Controlled release of iodine from cross-linked cyclodextrin metal-organic frameworks for prolonged periodontal pocket therapy.

Effective therapeutic system to periodontitis was designed using cross-linked cyclodextrin metal-organic framework (COF) as carrier for iodine and further suspended in hydroxyethyl cellulose gel as I2@COF-HEC hydrogel. Inclusion of iodine within the COF was demonstrated by SR-FTIR spectral and characteristic DSC and TGA changes. Molecular modelling identified the interaction of iodine with both COF central cavity and individual cyclodextrin moieties of COF. In vitro results of study demonstrated that iodine release in artificial saliva from I2@COF-HEC hydrogel could be extended up to 5 days, which was slower than I2@COF particles. Using an in vivo rat model of periodontitis, micro-computed tomography of alveolar bone morphology demonstrated that I2@COF-HEC hydrogel showed similar effects in decreasing periodontal pocket depth and alveolar bone resorption to minocycline ointment, a periodontitis antibiotic. The I2@COF-HEC hydrogel is a novel local delivery device of iodine as a broad spectrum antimicrobial use for treatment of periodontitis.

Polyvinylpyrrolidone microneedles for localized delivery of sinomenine hydrochloride: preparation, release behavior of in vitro & in vivo, and penetration mechanism.

Sinomenine (SIN) is an anti-inflammatory alkaloid derived from Sinomenium acutum, and the products sinomenine hydrochloride (SH) tablets and injections have been marketed in China to treat rheumatoid arthritis (RA). Oral administration of SH has shortcomings of gastrointestinal irritation and low bioavailability. The injection may require professional training and higher cost. It is of interest to develop an alternative form that is easier to administer and avoids the first-pass metabolism. In this study, SH-loaded dissolving microneedles (SH-MN) were fabricated using polyvinyl pyrrolidone and chondroitin sulfate with a casting method. In percutaneous permeation studies of In vitro, the cumulative permeation and permeation rate of SH-MN were 5.31 and 5.06 times higher than that of SH-gel (SH-G). In percutaneous pharmacokinetic studies, the values of the area under the curve after administration of SH-MN in the skin and blood were 1.43- and 1.63-fold higher than that of SH-G, respectively. In percutaneous absorption studies, SH-MN could absorb into tissue fluid; and dissolve after skin penetration. The drug was released along the channel and spread to surrounding skin tissue. After 4 h, the needle tip was almost completely dissolved, and the drug could penetrate to a depth of 200 µm under the skin. These results demonstrate that the SH-MN is an effective, safe, and simple strategy for transdermal SH delivery.

Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide.

The purpose of this study was to develop and evaluate triptolide-loaded cubic and hexagonal liquid crystals for transdermal drug delivery systems (TDDSs). We prepared and characterized triptolide-loaded lyotropic liquid crystals and evaluated for their percutaneous permeation properties in vitro and in vivo. We then used the adjuvant arthritic rat model and HaCaT cells to analyze the pharmacodynamics and conduct cell-stimulating studies of these liquid crystals. The optimized preparations were identified as cubic and hexagonal phase structures, respectively. Moreover, the in vitro percutaneous penetration studies demonstrated that compared to the homemade triptolide gel, cubic and hexagonal liquid crystals could significantly increase the percutaneous cumulative penetration of drugs within 48 h. Besides, the results of skin-blood synchronous microdialysis showed that the triptolide concentration in skin was higher than that in blood, and the cubic and hexagonal liquid crystals significantly increased the bioavailability of triptolide. Triptolide-loaded cubic and hexagonal liquid crystals presented excellent anti-arthritic effects, alleviating paw swelling and inhibiting inflammation by downregulating the levels of TNF-α and IL-1ß. In vitro cell-stimulating studies displayed that triptolide-loaded cubic and hexagonal liquid crystals exhibited no obvious toxicity, which exhibited that triptolide-loaded cubic and hexagonal liquid crystals were remarkable biocompatibility. Collectively, triptolide-loaded cubic and hexagonal liquid crystals represented a promising candidate for rheumatoid arthritis therapy.