RESUMO
The engineering of multifunctional surgical bactericidal nanofibers with inherent suitable mechanical and biological properties, through facile and cheap fabrication technology, is a great challenge. Moreover, hernia, which is when organ is pushed through an opening in the muscle or adjacent tissue due to damage of tissue structure or function, is a dire clinical challenge that currently needs surgery for recovery. Nevertheless, post-surgical hernia complications, like infection, fibrosis, tissue adhesions, scaffold rejection, inflammation, and recurrence still remain important clinical problems. Herein, through an integrated electrospinning, plasma treatment and direct surface modification strategy, multifunctional bactericidal nanofibers were engineered showing optimal properties for hernia repair. The nanofibers displayed good bactericidal activity, low inflammatory response, good biodegradation, as well as optimal collagen-, stress fiber- and blood vessel formation and associated tissue ingrowth in vivo. The disclosed engineering strategy serves as a prominent platform for the design of other multifunctional materials for various biomedical challenges.
Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis , Gelatina/farmacologia , Hérnia Abdominal/cirurgia , Herniorrafia/instrumentação , Metacrilatos/farmacologia , Nanofibras , Poliésteres/farmacologia , Infecção da Ferida Cirúrgica/prevenção & controle , Alicerces Teciduais , Animais , Antibacterianos/química , Modelos Animais de Doenças , Gelatina/química , Hérnia Abdominal/patologia , Metacrilatos/química , Camundongos , Células NIH 3T3 , Nanomedicina , Poliésteres/química , Ratos , Infecção da Ferida Cirúrgica/microbiologia , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: In recent years, numerous bacteria have become resistant to conventional antibiotics. Fortunately, an increasing body of research indicates that through the addition of specific metabolites (like sugars), the antibacterial activity of certain drugs can be enhanced. A new type of self-assembled nano-peptide amphiphile (SANPA) was designed in this study to treat antibiotic-resistant bacterial infections and to reduce the use of antibiotics. METHODS: Here, SANPAs were self-assembled into nanorod structures with a diameter of ca. 10.5 nm at concentrations greater than the critical micelle concentration (CMC) of 44.67 µM. Both Gram-positive and Gram-negative bacteria were treated with SANPAs with fructose supplementation. RESULTS: After a 30-min fructose pre-incubation, SANPAs reduced bacteria growth relative to non-fructose treatments at all concentrations. Cytotoxicity assays indicated that the presence of fructose seemed to slightly ameliorate the cytotoxic effect of the treatment on model human fetal osteoblasts (or bone-forming cells) and human dermal fibroblasts. CONCLUSION: We demonstrated here that SANPAs-like nanomaterials have a promising potential to treat antibiotic-resistant bacteria, especially when added to fructose, potentially limiting their associated infections.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Frutose/farmacologia , Peptídeos/química , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Células Cultivadas , Escherichia coli/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Frutose/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Peptídeos/farmacologiaRESUMO
In this study, a newly liposomal formulation of camptothecin (CPT) based on the dimeric camptothecin glycerophosphorylcholine (di-CPT-GPC) prodrug was developed. The di-CPT-GPC prodrug was synthesized through the heterogeneous conjugation of camptothecin-20 succinate with glycerophosphorylcholine. It undergoes assembly to form liposomes without any excipient through the thin film hydration method, which, confirmed by dynamic light scattering (DLS), have an average diameter of approximately 165⯱â¯5â¯nm. Observations on cryogenic transmission electron microscopy (cryo-TEM) demonstrated that the liposomes possess a typical multilamellar vesicle structure with a bilayer thickness of approximately 4â¯nm. The liposomes with a CPT loading up to 62â¯wt% maintained good stability in simulated physiological fluid. This can be attributed to the protection of the liposomes having CPT groups sequestered within the bilayer interior. Moreover, the in vitro release behavior of di-CPT-GPC liposomes was monitored using different media. The results showed that the liposomes could dissociate and sustainably release free active form CPT in a weak acidic environment. In vitro anticancer activity tests indicated that di-CPT-GPC liposomes had comparable cytotoxicity to the parent drug against MCF-7, HeLa and HepG-2 cells. Finally, a preliminary in vivo antitumor evaluation revealed that the liposomes inhibited tumor growth. Taken together, the di-CPT-GPC assembled liposomes with high drug loading could be a promising nanoformulation of CPT.