ABSTRACT
BACKGROUND: Retinoids represent an old class of bioactives used in the treatment of different skin pathologies (such as acne and psoriasis) and in the treatment of many tumors. Unfortunately, they present several side effects, i.e., burning of skin and general malaise after systemic administration and they are very unstable after exposition to light. METHODS: One of the most promising new approaches for reducing the side effects of retinoids while improving their pharmacological effect is the use of drug-delivery devices. This review explains the current status of retinoid drug transport, which has been developing over the last few years, explaining the modification of their biopharmaceutical properties in detail after encapsulation/inclusion in vesicular and polymeric systems. RESULTS/CONCLUSION: Different colloidal and micellar systems containing retinoid drugs have been realized furnishing important potential advancements in traditional therapy.
Subject(s)
Drug Carriers , Drug Delivery Systems/methods , Retinoids/administration & dosage , Retinoids/pharmacokinetics , Animals , Humans , Liposomes , Models, Molecular , Nanoparticles , Polymers , Retinoids/chemistryABSTRACT
BACKGROUND: The skin is the largest organ of our body and acts as a protective barrier with sensory and immunological functions. Its peculiar structure influences the passage of bioactives and only its modulation can facilitate the drug dermal/transdermal diffusion. In the past few years research in this field has assured better use of this application area. METHODS: One of the most promising approaches is the use of drug delivery devices; this review explains the state of the art of drug transport through the skin by means of vesicular (classic liposomes, Transfersomes, niosomes and ethosomes) and particulate systems. RESULTS/CONCLUSION: Colloidal drug delivery systems are important in the field of drug delivery systems as their different characteristics make them suitable for various purposes.
Subject(s)
Administration, Topical , Colloids/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Skin Absorption/physiology , Animals , Humans , Liposomes , Nanoparticles , Skin/chemistryABSTRACT
During follow-up of anemic hemodialysis patients (HDP) treated with recombinant human erythropoietin (rHuEpo), it was noticed that in five HDP, some time after suspension of rHuEpo, hemoglobin (Hb) levels remained at acceptable levels. A metabolic block of the pentose phosphate shunt (PPS) has been described in HDP, which leads to increased oxidative damage of red blood cell (RBC) membranes and increased susceptibility to hemolysis. The increased production of short-chain fatty aldehydes, including malonyldialdehyde (MDA), is an appropriate index of oxidative damage. This study aimed to verify whether the maintenance of acceptable levels of Hb was related to a change in RBC membrane oxidative damage and pentose phosphate shunt activity. In the five HDP in question who required rHuEpo (150 U/kg/week) for severe anemia (Hb = 7.48 +/- 0.95 g/dl), after a stable level of Hb > 10 g/dl was reached for at least 1 month, rHuEpo treatment was stopped. Hb levels remained adequate (Hb = 10.68 +/- 0.77 g/dl) after 14.6 +/- 7.64 months. The oxidative damage was evaluated by measuring RBC MDA (microgram/ml packed RBC) basal levels, and PPS activity by measuring MDA levels after incubation with ascorbate and cyanide (delta % RBC MDA production). Ten anemic HDP not treated with rHuEpo were used as controls (Hb = 8.12 +/- 1.32 g/dl). It was found that the maintenance of adequate levels of serum Hb after suspension of rHuEpo therapy is related to a decrease in RBC membrane oxidative damage (RBC MDA HDP = 2.40 +/- 0.41 vs. RBC MDA controls = 18.23 +/- 6.56; P < 0.005) in consequence of the normalization of pentose phosphate shunt activity.
Subject(s)
Erythrocyte Membrane/metabolism , Erythropoietin/administration & dosage , Pentose Phosphate Pathway , Renal Dialysis/adverse effects , Aged , Anemia/blood , Anemia/drug therapy , Anemia/etiology , Erythrocyte Count , Female , Hemoglobins/metabolism , Hemolysis , Humans , Lipid Peroxidation , Male , Malondialdehyde/blood , Middle Aged , Oxidation-Reduction , Uremia/complications , Uremia/therapySubject(s)
Kidney Transplantation/physiology , Adolescent , Child , Creatinine/blood , Female , Glomerular Filtration Rate , Graft Rejection/physiopathology , Graft Survival , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Male , Natriuresis , Phosphates/metabolism , Time FactorsABSTRACT
In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.
