ABSTRACT
Cutaneous wound healing is a complex process that leads the skin reparation with the formation of scar tissue that typically lacks skin appendages. This fact drives us to find new strategies to improve regenerative healing of the skin. This study outlines, the contribution of colloidal silica particles and oligourethane crosslinking on the collagen material properties and the effect on skin wound healing in rats. We characterized the gel properties that are key forin-situgelation, which is accomplished by the latent reactivity of oligourethane bearing blocked isocyanate groups to crosslink collagen while entrapping silica particles. The swelling/degradation behavior and the elastic modulus of the composite gel were consistent with the modification of collagen type I with oligourethane and silica. On the other hand, these gels were characterized as scaffold for murine macrophages and human stem cells. The application of a composite gel dressing on cutaneous wounds showed a histological appearance of the recovered skin as intact skin; featured by the epidermis, hair follicles, sebaceous glands, subcutaneous adipose layer, and dermis. The results suggest that the collagen-based composite dressings are promising modulators in skin wound healing to achieve a regenerative skin closure with satisfactory functional and aesthetic scars.
Subject(s)
Collagen Type I , Silicon Dioxide , Animals , Bandages , Cicatrix , Collagen/pharmacology , Gels , Mice , Rats , Wound HealingABSTRACT
AIM: The present study was focused to evaluate the anticonvulsant effects of phenytoin (PHT) loaded in the silica core of iron oxide nanoparticles (NPs) in an animal model with pharmacoresistant seizures. MATERIALS & METHODS: PHT-loaded NPs were synthesized and characterized. The anticonvulsant effects of PHT-loaded NPs were investigated in rats with pharmacoresistant seizures associated with brain P-glycoprotein (P-gp) overexpression. RESULTS & CONCLUSION: In P-gp-overexpressing rats, administration of PHT-loaded NPs resulted in reduced prevalence of clonus (40% p < 0.05) and tonic-clonic seizures (20%; p < 0.02). These effects were not evident when animals were treated with PHT not loaded in the NPs. The results obtained support the notion that NPs can be used as drugs carriers to the brain with pharmacoresistant seizures.
Subject(s)
Drug Resistance/drug effects , Nanoparticles/chemistry , Phenytoin/chemistry , Seizures/drug therapy , Animals , Anticonvulsants/therapeutic use , Disease Models, Animal , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Ferric Compounds/administration & dosage , Ferric Compounds/chemistry , Humans , Nanoparticles/administration & dosage , Phenytoin/administration & dosage , Rats , Seizures/pathology , Silicon Dioxide/administration & dosage , Silicon Dioxide/chemistryABSTRACT
Epilepsy is one of the most common chronic neurological disorders. Furthermore, it is associated to diminished health-related quality of life and is thus considered a major public health problem. In spite of the large number of available and ongoing development of several new antiepileptic drugs (AEDs), a high percentage of patients with epilepsy (35-40%) are resistant to pharmacotherapy. A hypothesis to explain pharmacoresistance in epilepsy suggests that overexpression of multidrug resistance proteins, such as P-glycoprotein, on the endothelium of the blood brain barrier represents a challenge for effective AED delivery and concentration levels in the brain. Proven therapeutic strategies to control pharmacoresistant epilepsy include epilepsy surgery and neuromodulation. Unfortunately, not all patients are candidates for these therapies. Nanotechnology represents an attractive strategy to overcome the limited brain access of AEDs in patients with pharmacoresistant epilepsy. This manuscript presents a review of evidences supporting this idea.
Subject(s)
Drug Carriers/therapeutic use , Epilepsy/drug therapy , Epilepsy/physiopathology , Models, Biological , Multidrug Resistance-Associated Proteins/metabolism , Nanoparticles/therapeutic use , Epilepsy/metabolism , HumansABSTRACT
Efflux transporter and enzyme overexpression can be induced by certain antiepileptic drugs. Phenytoin (PHT) is at the same time substrate and inducer of CYP2C isoenzymes and efflux carriers. Its inductive effect has been postulated to be concentration and time-dependent. Since verapamil (VPM) is a well known substrate and inhibitor of P-glycoprotein, its administration could modify PHT systemic exposure. The objective of this work was to determine if single doses (40mg/kg) of VPM might change PHT body fate in the same way when given at the beginning or several days after 100mg/kg of PHT daily doses were started. Both drugs were administered intraperitoneally to female Sprague Dawley rats. VPM increased plasma PHT concentrations after one day of treatment, while a decrease in PHT plasma exposure was observed when VPM was added at the fifth day of the antiepileptic treatment. These results suggested that VPM would have different impact on PHT pharmacokinetics, depending on the level of expression of both efflux transporters and enzymes. Before the hepatic cells could acquire a high content of enzymes due to the inductive effect of PHT dosing, VPM decreased the predominant intestinal clearance of PHT. But, once the enzymatic machinery at the hepatocyte became more important than that at the intestine, although ineffective because of the high hepatobiliary efflux transporter overexpression, VPM blockade from the liver resulted in an increased total PHT clearance.
