ABSTRACT
Temozolomide is a drug approved for treating glioblastomas, which has 100% oral bioavailability but gets degraded at physiological pH thus having very short half-life and only 20-30% brain bioavailability. Due to its amphiphilic nature, reported nanoformulations exhibits poor drug loading. The objective of this work was to formulate lipid-based drug delivery systems to enhance the brain bioavailability by prolonging the drug release and circulation time of the drug to overcome the limitations of the existing therapies and possible reduction of side effects. The size of the nanocarriers obtained was less than 300 nm and the PDI obtained was less than 0.3. The designed formulation showed higher entrapment efficiency as compared to the other reported nanocarriers of temozolomide. The designed formulations showed prolonged drug release from 12 to 20 h compared to 6 h for the pure drug. About 95% of the pure drug was degraded at plasma pH at the end of 12 h, whereas only 68% and 77% was degraded when entrapped inside the lipid crystal nanoparticles and proliposomes respectively. Further, pharmacokinetic and animal studies can confirm the potential of these for improvement of brain bioavailability.
Subject(s)
Liposomes , Nanoparticles , Animals , Hydrogen-Ion Concentration , Lipids , Particle Size , TemozolomideABSTRACT
Brain disorders, a diverse range of conditions comprising of neurological and psychiatric conditions, are the leading cause of disability, severely affect the quality of life, and in many cases lead to mortality. The prime challenge in treatment of brain disorders is to deliver therapeutics by overcoming the blood-brain barrier (BBB), a unique anatomical and physiological barrier which restricts the passage of a number of molecules, proteins, and cells from the bloodstream. Lipid nanoparticles have emerged as promising drug delivery systems primarily because of biodegradability, low toxicity potential, and the ability to cross physiological barriers especially the BBB even without surface modifications.In this chapter we discuss the preparation and characterization of nanostructured lipid carriers of temozolomide, a chemotherapeutic drug. Evaluation of pharmacokinetics and biodistribution of the nanocarrier system in rats revealed improved delivery of the chemotherapeutic agent to the brain with the potential of lesser side effects.
Subject(s)
Brain Diseases/metabolism , Drug Carriers/administration & dosage , Drug Delivery Systems/methods , Lipids/chemistry , Nanoparticles/administration & dosage , Temozolomide/administration & dosage , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/pharmacokinetics , Blood-Brain Barrier , Brain Diseases/drug therapy , Chromatography, Liquid , Drug Carriers/chemistry , Drug Carriers/metabolism , Dynamic Light Scattering , Male , Microscopy, Electron, Scanning , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Particle Size , Rats , Rats, Wistar , Temozolomide/adverse effects , Temozolomide/chemistry , Temozolomide/pharmacokinetics , WorkflowABSTRACT
Nanostructured lipid carriers (NLC), comprises of a blend of solid and liquid lipids which results in a partially crystallized lipid system and imparts many advantages over solid lipid nanoparticles such as enhanced drug loading capacity, drug release modulation flexibility and improved stability. NLC have found numerous applications in both pharmaceutical and cosmetic industry due to ease of preparation, the feasibility of scale-up, biocompatibility, non-toxicity, enhanced targeting efficiency and the possibility of site-specific delivery via various routes of administration. This review highlights the NLC with focus on the structure, the various fabrication techniques used and the characterization techniques which are critical in the development of a suitable and stable formulation. The review also provides an insight into the potential of NLC as site-specific delivery systems and the therapeutic applications explored via various routes of administration.
