Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters.

OBJECTIVE: To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces. DESIGN: Experimental trial. METHODS: Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens with Staphylococcus epidermidis or Staphylococcus aureus culture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria. RESULTS: Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective against Candida species and Pseudomonas aeruginosa. Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged with S aureus 7 and 14 days' postimplant (P<.05). Repeated in vitro exposure of S epidermidis culture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistant S epidermidis in vivo (P<.05). CONCLUSIONS: Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device.

In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices.

The risk of development of resistance in Staphylococcus epidermidis to the antibiotics and antiseptics impregnated in central venous catheters was evaluated. The culture was passaged 10-20 times through subinhibitory concentrations of different antimicrobials, singly and in combination, and the MIC of each antimicrobial before and after passage was compared. There was a 10- to 16-fold increase in the MIC of the combination of minocycline and rifampicin, while no significant increase in the MIC of minocycline alone was seen. The MIC of rifampicin was 25,000-fold higher against strains passaged through rifampicin alone (as compared with that for the original strain), while the increase was only 80-fold when it was combined with minocycline for passage. There was no substantial change in susceptibility to the antiseptic chlorhexidine when used alone or in combination with either silver sulphadiazine or triclosan (the MIC of triclosan alone increased eight-fold). In time-kill studies, synergy was observed between chlorhexidine and both triclosan and silver sulphadiazine. Zone of inhibition tests of catheters impregnated with minocycline and rifampicin showed that their activity against rifampicin-resistant strains was lower than that against the susceptible strain. On the other hand, the activity of the antiseptic (chlorhexidine and silver sulphadiazine) catheters against the rifampicin-resistant and -susceptible strains was similar. Although this study indicates that antibiotic catheters may be at a higher risk of being colonized by antibiotic-resistant bacteria, the implications of these results in clinical settings need to be determined.