| Popis: |
Chronic wounds are difficult to heal and exhibit physiological features including prolonged inflammatory phase, mixed bacterial flora resistance and formation of biofilms, ineffectiveness of topical antimicrobials and high volumes of wound exudate. Polymeric gels of Polyox (POL) and blends of POL with carrageenan (CAR), chitosan (CS), hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA) in different weight ratios were used to prepare films by the solvent casting technique and evaluated using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier transform spectroscopy (FTIR). The same gels were analysed using DSC to develop an optimum lyophilisation cycle with or without an annealing step to obtain freeze dried wafers of POL-CAR and POL-SA. Films prepared from POL were non-transparent and showed spherulitic crystallisation, however POL blends with CAR and SA (75/25 and 50/50 weight ratios respectively) showed improved flexibility and transparency with reduced spherulitic crystallisation (i.e. homogeneous surface) through hydrogen bonding between POL and/or CAR and SA. Addition of annealing step -25°C resulted in formulations with porous surface morphology for both POL-CAR and POL-SA wafers. Annealing (wafers) and addition of glycerol (GLY) (films) resulted in improved mechanical properties expected to withstand the mechanical stresses occurring during day-to-day activities and whilst flexible enough to prevent potential damage to newly formed tissue. Tough and flexible films were obtained by the addition of 9%w/w and 20% w/w GLY in POL-SA and POL-CAR respectively. Further, the POL-CAR and POL-SA films and wafers were loaded with 5-15%w/w of diclofenac (DLF) and 15-30% w/w of streptomycin (STP). Furthermore POL-CAR and POL-SA blank (BLK) and drug loaded (DL) films and wafers were analysed for swelling, mucoadhesion (in presence of normal and viscous simulated wound fluid), in vitro drug dissolution and anti-bacterial activity and compared against marketed medicated wound dressings. Addition of drug (STP and DLF) resulted in fair transparency of films and decreased porosity of wafers with existence of sodium sulphate which affected general performance of the films and wafers in terms of swelling, mucoadhesion, and antimicrobial activity. BLK plasticised (GLY) films and BLK annealed wafers showed higher swelling capacities compared to DL films and wafers. Neither DL films nor wafers showed 100 % release of the incorporated STP and DLF due to the formation of sodium sulphate which reduced hydration. Findings also showed that POL-SA films and wafers were effective against normal exudate whereas POL-CAR films and wafers were effective for viscous exudate to achieve better bioavailability and prolonged retention time. Multivariate data analysis of mucoadhesion showed slower rate of mucin diffusion into POL-CAR films and wafers compared to POL-SA films and wafers. The formulated films, wafers and marketed dressing showed antibacterial efficacy against 105 CFU/ml of S. aureus, P. aeruginosa and E. coli. STP and DLF present in both films and wafers acted synergistically and showed better antimicrobial activity than marketed dressings. Film dressing allows ease of application and due to fair transparency and flexibility whereas wafer dressings are useful to control exudate and both can maintain a moist environment. Combination of STP and DLF within a single dressing is expected to help to treat and prevent wound infections whereas DLF can help to relieve pain and inflammation associated with injury. |
