In vitro and in vivo investigation for optimization of niosomal ability for sustainment and bioavailability enhancement of diltiazem after nasal administration

Abstract

Diltiazem hydrochloride (DTZ) is a calcium channel antagonist depicted by extensive first pass metabolism and low oral bioavailability. The aim of this work was to develop niosomes for potential nasal delivery of DTZ. Niosomes protect hydrophilic drugs inside their core while nasal route offers both rapid onset and evasion of first-pass metabolism. Niosomes were prepared using a combination of Span 60 or Brij-52 with cholesterol (CHOL) in different molar ratios followed by determination of entrapment efficiency, particle size and in vitro drug release. A parallel design was adopted to evaluate the pharmacokinetic performance of DTZ-loaded niosomes in male Wistar rats. Non-compartmental analysis was performed where C max , T max , t 1/2 , MRT, area under the release curve (AUC) and K e were assessed. The prepared niosomes were spherical with mean particle size 0.82-1.59 mm. Span 60-cholesterol niosomes (1:1 molar ratio) showed the highest entrapment and release efficiencies. In vivo study revealed an increase in MRT, t 1/2 and AUC with a decrease in K e . In conclusion, nasal niosomal formulation of DTZ expressed suitable pharmacokinetic parameters and bioavailability through prolonged duration of action inside the body as well as low rate of elimination depicting a promising alternate to the conventional oral route.

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

“…Niosomes have larger PS so they show lower PDI. On the other hand, spanlastics which have smaller PS show larger PDI that may be due to the difference in composition between both types of vesicular structures [33].…”

“…While the spanlastics showed lower EE than niosomes this may refer to the presence of span 60 and absence of cholesterol. Span 60 has a low HLB value (5.3), long carbon chain (C16) and it has a high phase transition temperature which decreases the leakage and the fluidity of the bilayer that leads to lower EE [33,37].…”

Intranasal Nanoparticulate Systems as Alternative Route of Drug 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]. The study of using intranasal niosomes for vaccination with glycoprotein B of herpes simplex virus type 1 has shown in vitro controlled release and in vivo elicited plasma glycoprotein antibodies (IgG) and systemic T helper cells [149].…”

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

“…Studies showed that zidovudine (BCS Class III) niosomes prepared with Tween 80 as surfactant and DCP as stabilizer (-ve charge-inducer) effectively entrapped high amounts of drug and released 88.72% of drug over 12 h [13]. Ammar HO et al investigated that Diltiazem (BCS Class I) niosomes prepared with span 60 and Cholesterol (1:1 molar ratio) showed maximum entrapment efficiency and drug release on in-vitro investigation and in-vivo study exhibited an increase in MRT, t1/2 and AUC with a decrease in Ke [14].…”