Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment

Abstract

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers’ act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine’s low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor’s effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm 2 ) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma’s rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.

A review of important heavy metals toxicity with special emphasis on nephrotoxicity and its management in cattle

“…The oxidative stress that Pb exposure induces appears to have a detrimental effect on the kidneys of cattle, leading to the development of renal toxicity ( 118 , 119 ). Cattle exposed to Pb have higher levels of lipid peroxidation in their kidneys ( 23 , 120 ). Long-term Pb exposure causes the kidney to produce lipid peroxidation and free radicals, which lead to a loss of membrane permeability and the inactivation of components of tubular cells ( 121 , 122 ).…”

“…Oxidative stress as a mechanism of Pb toxicity in the kidney shows that Pb exposure causes an increase in apoptosis in the kidney ( 126 ). The frequency of apoptotic bodies inside proximal tubular cells increased after 12 weeks of continuous lead acetate therapy ( 23 , 127 ). Therefore, it is conceivable that Pb poisoning affects the gene expression of proteins involved in apoptosis.…”

“…Renal function impairment occurs as a result of persistent lead buildup in the body. It was concluded that the formation of renal toxicity due to environmental lead exposure results in major pathological lesions on the kidney of cattle that appears to be influenced by oxidative stress ( 23 , 132 , 133 ).…”

Antiepileptic drug concentration detection based on Raman spectroscopy and an improved snake optimization-convolutional neural network algorithm

“…The improvement of human health monitoring and disease treatment capabilities is of great importance to the stability and progress of human society. Diseases such as uterine fibroids, 1 diabetes, 2 strokes, 3 and epilepsy 4 have complex detection methods and treatment difficulties awaiting problem-solving. Several major antiepileptic drugs, such as oxcarbazepine, carbamazepine, and lamotrigine, 5–7 are used for human treatment depending on the different seizure mechanisms.…”

Alterations in brain network functional connectivity and topological properties in DRE patients

“…For patients with DRE, finding potential therapeutic targets and intervention strategies can effectively control seizures and improve the quality of life of patients ( 4 ). In this context, functional network analysis provides a powerful research tool.…”