Effect of a combination of mometasone furoate, levofloxacin, and retinyl palmitate with an in situ gel-forming nasal delivery system on nasal mucosa damage repair in an experimental rabbit model.

BACKGROUND: In this study a combination of Mometasone Furoate (MF)+Levofloxacin hemihydrate (LH)+Retinyl palmitate (RP) with an in situ gel-forming delivery system was evaluated at different stages of nasal mucosal damage repair in a rabbit maxillary sinus model. METHODS: In this study, 28 rabbits were included and assigned randomly to four groups. In all rabbits, a standard ostium was opened in the medial wall of the maxillary sinus by using a drill. Two different subsequently prepared gels with an in situ gel-forming delivery system were used. Of these 14 nasal cavities, combination 1 (active combination) was applied daily to 5, combination 2 (placebo) to 5, while 4 did not receive any pharmaceutical treatment. The diameter of the ostium was measured. Histopathological assessment was performed. RESULTS: After 2, 3 and 4 weeks, the ostium diameter was significantly wider in the group where gel 1 had been applied compared to both the placebo group and control group. In the group treated with gel 1, after 2, 3 and 4 weeks the presence of superficial cilia was significantly greater, surface epithelium significantly less. In the 4th week, histologic scores for fibroblastic proliferation and vascular proliferation in the group treated with gel 1 were better than in either the control group or the placebo group. With gel 1, chronic inflammation parameters were also significantly lower than in the other groups. CONCLUSION: The MF+LH+RP mixture with an in situ gel-forming nasal delivery system applied for wound healing after FESS prevents the formation of stenosis and is favorable for proper wound healing.

In vitro release and In vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/ß-TCP scaffold for osteochondral tissue.

Biomimetic three-layered monolithic scaffold (TLS) intended for the treatment of osteocondral defects was prepared by using alginate, chitosan and ß-tricalcium phosphate (ß-TCP) to study drug release behavior of the alternative drug delivery system and to investigate the therapeutic efficacy of the scaffold. Dexamethasone sodium phosphate (Dex) as a model drug was incorporated into the scaffold by solvent sorption method and in vitro release studies were conducted. In addition, the scaffold was implanted into the defects formed in the trochlea of Sprague-Dawley rats to assess the healing potential of the TLS on the osteochondral defect against reference Maioregen® comparatively. The release studies showed that after an initial burst at 3rd h, dexamethasone is released slowly during a 72-h period. In vivo studies indicated that the TLS has good tissue biocompatibility and biodegradation rate and showed better results during osteochondral healing process compared to the reference. All results demonstrated that the alginate-chitosan/ß-TCP scaffold could be evaluated as a good candidate for osteochondral tissue applications.

Biocompatibility of biomimetic multilayered alginate-chitosan/ß-TCP scaffold for osteochondral tissue.

Biomimetic three-layered monolithic scaffold (TLS) intended for treatment of osteochondral defects was fabricated by using freeze drying method. The multilayered material was prepared with chitosan (C) and alginate (A) polyelectrolyte complex (CA/PEC) as a cartilaginous layer, a combination of CA/PEC (60 wt%) and ß-tricalcium phosphate (ß-TCP) (40 wt%) as an intermediate layer and a combination of CA/PEC (30 wt%) and ß-TCP (70 wt%) as a subchondral layer in order to mimic the inherent gradient structure of healthy osteochondral tissue. Characterization of the scaffolds was performed using Fourier transform infrared (FT-IR) spectroscopy analysis, swelling and scanning electron microscopy (SEM) tests. In vitro cytotoxicity assay with L929 cells and EpiDerm skin irritation test (SIT) using the EpiDerm reconstructed human epidermal (RHE) model were performed to analyze biocompatibility of the scaffolds. Characterization results showed that there were strong ionic interactions among chitosan, alginate and ß-TCP and the layers showed interconnected porous structure with different swelling ratios. The relative cell viability and SIT results were greater than 70% indicating that the scaffolds are considered nontoxic according to the International Organization for Standardization (ISO) standard. All results taken together, biomimetic TLS can be considered to be suitable for osteochondral applications.