Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

Abstract

Objective: To prepare and optimize the topical elastic liposome (EL)-loaded carbopol-980 gel of 5-Fluorouracil (5-FU) containing permeation enhancers (azone, propylene glycol (PG) and lauryl alcohol (LA)) and further evaluation for permeation flux of 5-FU, the activation energy and irritation in the rat skin. Methods: EL formulations were prepared using phosphatidylcholine and varied surfactants (Span 60, Span 80 and Tween-80) by rotator evaporation method and optimized by experimental design. In vitro characterizations dictated the EL containing Span 80 (lipid:surfactant ¼ 7:3) (EL3-S80) for further optimization of gel. Different gel formulations (5% w/w) with varying concentration (1-3%) of permeation enhancers were prepared and evaluated for viscosity, spreadability, the 5-FU permeation and deposition. The activation energy using the Franz diffusion cell and the plausible irritation using the Draize test were assessed on the albino rat and rabbit, respectively. Results and discussion: EL3-S80 was selected as an optimized EL owing to maximum desirability (0.99) and enhanced 5-FU flux (187.86 ± 14.1 mg/cm 2 /h). EL3-S80 suspension loaded gels (0.5%) revealed reduced viscosity leading to higher spreadability than blank gel. EL containing 3% azone in gel, EL containing 3% LA in gel and EL containing 3% PG in gel portrayed 187.86 ± 14.1, 117.7 ± 13.4 and 106.7 ± 7.3 mg/cm 2 /h as enhanced 5-FU flux values, respectively as compared to drug solution (8.8 ± 0.76 mg/cm 2 /h). Furthermore, reduced value of activation energy (2.63-folds) and the non-irritancy of gel could be effective and safe. Conclusion: ELA-3 gel formulation could be used as an effective and economic gel in cutaneous cancer and skin-related keratoses.

Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of Amphotericin B

“…Moreover, PEG-400 and LAB have been shown as an effective permeation enhancer by extracting the SC lipids to disrupt the hydrophobic SC barrier leading to facilitated permeation. The exerted enhanced permeation rate for the topical release of AmB formulation from the AmB-NE6 may be due to obviously possible mechanisms (Teichmann et al, 2007;Hussain et al, 2015. Furthermore, amount of the drug deposited into the skin was portrayed in Figure 7 suggesting maximum drug deposition by AmB-NE6 (74 ± 5.6%) as compared to DS (8.8 ± 1.2%) and Fungisome Õ (45 ± 3.4%) which could be due to formulation-mediated enhanced permeation flux .…”

“…Blank NE and drug-loaded formulations were subjected to characterize for particle size and size distribution followed with zeta potential measurement using the dynamic light scattering (DLS) technique (Malvern Zetamaster, ZEM 5002, Worcestershire, UK) as reported method (Attwood et al, 1992;Hussain et al, 2015;Hussain & Singh, 2016). DLS is frequently employed method working on population-based particle size analysis.…”

Novel elastic membrane vesicles (EMVs) and ethosomes-mediated effective topical delivery of aceclofenac: a new therapeutic approach for pain and inflammation

“…The animals were then sacrificed by cervical dislocation; skin samples were removed and fixed in 10% formalin solution. The skin samples obtained were stained with hematoxylin and eosin and observed microscopically for any histopathological changes (Raza et al, 2013;Hussain et al, 2015a).…”

Elastic liposomes as novel carriers: recent advances in drug delivery

“…32 Similarly, itraconazole (IT) -due to high lipophilicity (log P.5.5), poor aqueous solubility (1 µg/mL), and relatively high molecular weight (~705 Da) -received attention from researchers for TD using ELs in the treatment of superficial or cutaneous fungal infections. 4,36 An IT-hydroxylpropyl-β-cyclodextrin complex loaded EL enhanced permeation across the skin and retained antifungal activity as compared to the plain DS. 51 Recently, poorly soluble and low-permeable AmB was investigated to treat cutaneous fungal infections and leishmaniasis.…”

“…Additionally, a considerable reduction in activation energy was found (2.63-fold lower than the DS after topical application to the skin). 36 Utreja et al investigated ELs for the TD of paclitaxel and characterized them with in vitro, ex vivo, and in vivo parameters, with comparisons against a marketed product. The paclitaxel-loaded ELs (6 mg/mL) showed a 10.8-and 15.8-fold higher in vitro skin permeation and deposition rate, respectively, as compared to DS.…”