ABSTRACT
Among lipid-based nanocarriers, multi-layered cochleates emerge as a novel delivery system because of prevention of oxidation of hydrophobic and hydrophilic drugs, enhancement in permeability, and reduction in dose of drugs. It also improves oral bioavailability and increases the safety of a drug by targeting at a specific site with less side effects. Nanostructured cochleates are used as a carrier for the delivery of water-insoluble or hydrophobic drugs of anticancer, antiviral and anti-inflammatory action. This review article focuses on different methods for preparation of cochleates, mechanism of formation of cochleates, mechanism of action like cochleate undergoes macrophagic endocytosis and release the drug into the systemic circulation by acting on membrane proteins, phospholipids, and receptors. Advanced methods such as calcium-substituted and ß-cyclodextrin-based cochleates, novel techniques include microfluidic and modified trapping method. Cochleates showed enhancement in oral bioavailability of amphotericin B, delivery of factor VII, oral mucosal vaccine adjuvant-delivery system, and delivery of volatile oil. In near future, cochleate will be one of the interesting delivery systems to overcome the stability and encapsulation efficiency issues associated with liposomes. The current limiting factors for commercial preparation of cochleates involve high cost of manufacturing, lack of standardization, and specialized equipments.
Subject(s)
Drug Compounding/methods , Drug Delivery Systems/methods , Lipid Bilayers/chemistry , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacokinetics , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Biological Availability , Calcium/chemistry , Chemistry, Pharmaceutical/methods , Drug Compounding/economics , Drug Stability , Microfluidics/methods , Particle Size , Vaccines/administration & dosage , Vaccines/chemistry , Vaccines/pharmacokinetics , beta-Cyclodextrins/chemistryABSTRACT
The objective of the present work was to engineer and characterize stable citric acid cross-linked microcomplex of the inclusion complexes of artemether with ß-cyclodextrin and Kollidon VA 64® with lumefantrine to release the drugs in controlled manner for effective combinational drug treatment in malaria. The microcomplex had a hydrodynamic diameter of 1047 ± 147 nm with surface charge of -19.7 ± 0.5 mV. The microcomplex showed high encapsulation efficiencies 85.6 ± 1.78% for artemether and 91.16 ± 2.21% for lumefantrine due to the lipophilic nature of drugs. In-vitro and in-vivo drug release studies showed the controlled release of artemether and lumefantrine for a period of 24 h.
Subject(s)
Antimalarials/chemistry , Artemisinins/chemistry , Drug Carriers/chemistry , Ethanolamines/chemistry , Fluorenes/chemistry , Malaria/drug therapy , Antimalarials/therapeutic use , Artemether , Artemisinins/therapeutic use , Citric Acid/chemistry , Drug Interactions , Drug Liberation , Ethanolamines/therapeutic use , Fluorenes/therapeutic use , Lumefantrine , Microspheres , Particle Size , Pyrrolidines/chemistry , Vinyl Compounds/chemistry , beta-Cyclodextrins/chemistryABSTRACT
Reverse or inverse docking is proving to be a powerful tool for drug repositioning and drug rescue. It involves docking a small-molecule drug/ligand in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analyses of the binding characteristics lead to ranking of the targets according to the tightness of binding. This process can potentially identify novel molecular targets for the drug/ligand which may be relevant for its mechanism of action and/or side effect profile. Another potential application of reverse docking is during the lead discovery and optimization stages of the drug-discovery cycle. This review summarizes the state-of-the-art and future prospects of the reverse docking with particular emphasis on computational molecular design.
