RESUMO
Hydrogels with the main objective of releasing mesalamine (5-aminosalicylic acid) in the colon in a modified manner were formulated in the present work using a free-radical polymerization approach. Different ratios of hyaluronic acid were cross-linked with methacrylic and acrylic acids using methylenebis(acrylamide). The development of a new polymeric network and the successful loading of drug were revealed by Fourier transform infrared spectroscopy. Thermogravimetric analysis demonstrated that the hydrogel was more thermally stable than the pure polymer and drug. Scanning electron microscopy (SEM) revealed a rough and hard surface which was relatively suitable for efficient loading of drug and significant penetration of dissolution medium inside the polymeric system. Studies on swelling and drug release were conducted at 37 °C in acidic and basic conditions (pH 1.2, 4.5, 6.8, and 7.4, respectively). Significant swelling and drug release occurred at pH 7.4. Swelling, drug loading, drug release, and gel fraction of the hydrogels increased with increasing hyaluronic acid, methacrylic acid, and acrylic acid concentrations, while the sol fraction decreased. Results obtained from the toxicity study proved the formulated system to be safe for biological systems. The pH-sensitive hydrogels have the potential to be beneficial for colon targeting due to their pH sensitivity and biodegradability. Inflammatory bowel disease may respond better to hydrogel treatment as compared to conventional dosage forms. Specific amount of drug is released from hydrogels at specific intervals to maintain its therapeutic concentration at the required level.
RESUMO
Background: Frequency of extended-spectrum-ß-lactamase-producing clinical isolates is increasing worldwide. This is a multi-center study which was aimed to check the frequency of third-generation cephalosporin resistance and distribution of the key genetic determinants of Extended-spectrum-ß-lactamase-producing Clinical isolates in Pakistan. Methods: A total of 2372 samples were processed in three tertiary care hospitals and one diagnostic research center of Lahore, Pakistan during Aug-2014 to Sep-2017. Analytical profile index (API 20-E) was used for biochemical characterization of isolates. Antibiotic susceptibility testing (AST) and third generation cephalosporin resistant (3GC-R) isolates were subjected to: double disc synergism test (DDST), combination disc test (CDST) and epsilometric test (E-test) for confirmation of ESBL-production. PCR amplification of isolates with plasmid and genomic DNA was performed. Amplicon sequences were checked for gene-variants and statistical analyses were performed to check the significance of data. Results: A total of 497/995 (50%) isolates including Escherichia coli 65% (n = 321), Klebsiella spp. 25% (n = 124) and Pseudomonas. 5% (n = 24), Enterobacter spp. 4% (n = 20) and Acinetobacter spp. 2% (n = 8) were screened as third generation cephalosporin resistant (3GC-R). Urine 56% (n = 278) followed by pus 20% (n = 99) and wound swab 6% (n = 29) were frequent sources. Incidence of ESBL-producers detected by combination disc test was 79% (n = 392). PCR revealed blaCTX - M (76%) gene followed by blaOXA (52%), blaTEM (28%) and blaSHV (21%) were most prevalent among ESBL-producers detected by CDST. blaCTX - M - 1(65%), blaOXA (78%) and blaTEM (57%) genes were carried on plasmids. Amplicon sequencing revealed blaCTX - M - 15 (75%), blaOXA - 1 (49%) and blaTEM - 1B (34%) and 21 (n = 28) isolates carried three genes in them. Conclusion: Prevalence of ESBL-producing isolates has increased 1.13 folds during study years. Isolates had high prevalence of ESBL-encoding blaCTXM - 15 gene and narrow spectrum blaOXA - 1 and blaTEM - 1B were also prevalent.