Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2³factorial design andin vivoevaluation in rabbits

Abstract

Context: Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. Objectives: To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Materials and methods: Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2 3 full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X 1 ), the amount of soya lecithin (X 2 ), and the amount of cremophor RH 40 (X 3 ) were selected as three independent variables. Results and discussion: The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm 2 /h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 À a) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Conclusions: Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine. KeywordsBioavailability study, 2 3 full factorial design, lacidipine, proniosomal gel transdermal delivery History

Fabrication of Anti-HSV-1 Curcumin Stabilized Nanostructured Proniosomal Gel: Molecular Docking Studies on Thymidine Kinase Proteins

“…The mean vesicle size of diluted proniosomes ranged from 161.55 ± 1.06 nm to 250.60 ± 1.27 nm with a low polydispersity index ( Table 1). The smaller vesicle size would allow for lowered skin irritation and enhanced skin penetration [34].…”

“…The observed permeation improvement of curcumin proniosomes could be attributed to the penetration enhancing capabilities of the included surfactants in the fabrication of proniosomes, which are known by their ability to increase fluidity, solubilize, and extract lipid component of the stratum corneum. Keratin interactions are considered as an additional mechanism through which the surfactants can exert penetration enhancing effects [34]. In addition, the formed niosomes also can enhance the permeability of drugs through structure modification of stratum corneum [64].…”

“…The %EE was carried out using the filtration method [34]. Curcumin proniosomes (0.1 g) were hydrated with distilled water (10 mL) and sonicated (30 min.).…”

Proniosomes derived niosomes: recent advancements in drug delivery and targeting

“…Another study manifested that proniosomes are flexible drug delivery carrier system having potential to deliver drugs effectively through transdermal route. Anti-hypersensitive drug lacidipine loaded transdermal proniosomes were produced by using cremophor RH as nonionic surfactant (Soliman et al, 2016). Rajabalaya et al (2016) successfully encapsulated oxybutynin chloride in proniosomes for its transdermal delivery in overactive bladder therapy.…”

Preparation and Optimization of Buccal Propranolol Hydrochloride Nanoethosomal Gel: A Novel Approach for Enhancement of Bioavailability

“…The enhancement ratio (Er) attributed to ethosome encapsulation was calculated by the following equation [27]: The data obtained from the permeation studies were kinetically analyzed and the order of drug permeation from the ethosomal gel was determined. Zero-and first-order kinetics as well as the Higuchi diffusion model was employed and the correlation coefficient values (R 2 ) were determined.…”