Formulation and Evaluation of Niosomal Nasal Drug Delivery System of Folic Acid for Brain Targeting

Abstract

Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drug delivery systems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625 µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4±1°C and 25±1°C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs.

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

“…Niosomes for intranasal application have been proposed to represent a promising approach for enhanced and controlled delivery. Intranasal folic acid niosomes intended for brain targeting have shown controlled ex vivo perfusion [147]. Regarding the systemic effects of intranasal niosomes, diltiazem-loaded niosomes have shown high half-life (T1/2 ) and enhanced AUC 0-∞ with a reduced elimination rate; such prolonged action for diltiazem is of great value compared to its low oral bioavailability due to extensive first-pass metabolism [148].…”

Niosomes as an Emerging Formulation Tool for Drug Delivery-a Review

“…In Griseofulvin niosomes, DCP imparts a negative charge to the bilayer vesicles as they are found to be more competent for drug delivery and provides stability to the system, prevents agglomeration and aggregation of vesicles [15]. Nagaraju Ravouru et al developed Folic acid (BCS Class IV) niosomes for brain targeting with span60 and cholesterol (stabilizing agent) in the ratio of 1:1 (50 mg: 50 mg), showed the entrapment efficiency of about 69.42% with better in-vitro drug release profile of 64.2% at the end of 12 h [16].…”

Diagnostic and therapeutic potentials of exosomes in CNS diseases

“…Numerous details will need to be considered during exosomal engineering and some lessons may be learned from the efforts that lead to the development of liposome-based thereapies, e.g. structural composition, viscosity and size of particles that affects number of functions, such as plasticity of the particles, response to osmotic shock, entrapment efficiency and drug release (Ravouru et al , 2013; Salama et al , 2012). …”