RESUMEN
Periodontitis comprises a chronic inflammation that is initiated by microbiota biofilm. If left untreated, periodontitis may lead to permanent tooth loss. Herein, we propose to design and improve a localized form of therapy comprising a chlorhexidine-impregnated hydrogel. Hydrogel films were prepared by varying the ratio between cellulose (MCC) and carboxymethylcellulose sodium (CMC) using the crosslinker epichlorohydrin (ECH). The hydrogel was loaded with chlorhexidine. Increasing the CMC ratio led to a reduction in the number of pores, an increase in their size, lower glass transition temperature (T g ), decreased Young's modulus, and increased film stretching and affected the time of release. Bacterial and fungal zones of inhibition showed similar activity and were not affected by the CMC and MCC ratio. Hydrogels loaded with chlorhexidine prevented the growth of S. oralis and C. albicans microorganisms and may provide a promising local delivery system for treating periodontitis.
Asunto(s)
Carboximetilcelulosa de Sodio/química , Clorhexidina/uso terapéutico , Metilgalactósidos/uso terapéutico , Periodontitis/tratamiento farmacológico , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Clorhexidina/farmacología , Liberación de Fármacos , Módulo de Elasticidad , Hongos/efectos de los fármacos , Vidrio/química , Humanos , Cinética , Metilgalactósidos/farmacología , Pruebas de Sensibilidad Microbiana , Resistencia a la Tracción , Temperatura de TransiciónRESUMEN
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somatostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the biostability of peptides. This is achieved through a number of mechanisms ranging from replacement of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation, peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The development of self-assembling peptides are paving the way for sustained release peptide formulations and already two such licensed examples exist, lanreotide and octreotide. The versatility and tunability of peptide-based products is resulting in increased translation of peptide therapies, however significant challenges remain with regard to their wider implementation. This review highlights some of the notable peptide therapeutics discovered to date and the difficulties encountered by the pharmaceutical industry in translating these molecules to the clinical setting for patient benefit, providing some possible solutions to the most challenging barriers.
Asunto(s)
Industria Farmacéutica , Péptidos/química , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacterias/efectos de los fármacos , Composición de Medicamentos , Humanos , Síndrome del Colon Irritable/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Péptidos/síntesis química , Péptidos/uso terapéutico , Extractos de Tejidos/uso terapéuticoRESUMEN
Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections.