Flexible nano-sized lipid vesicles for the transdermal delivery of colchicine; in vitro/in vivo investigation
El-Feky G.S.; El-Naa M.M.; Mahmoud A.A.
Date issued:
2019
Publisher:
Editions de Sante
Series Info:
Journal of Drug Delivery Science and Technology
49
Type:
Article
Keywords:
October University for Modern Sciences and Arts
,
University for Modern Sciences and Arts
,
MSA University
,
جامعة أكتوبر للعلوم الحديثة والآداب
,
Colchicine
,
In vivo study
,
Lipid vesicles
,
Transdermal
,
?-cyclodextrin
,
beta cyclodextrin
,
colchicine
,
drug carrier
,
transfersome
,
unclassified drug
,
animal experiment
,
animal model
,
Article
,
controlled study
,
drug bioavailability
,
drug delivery system
,
drug efficacy
,
drug formulation
,
drug penetration
,
drug release
,
drug solubility
,
elasticity
,
ex vivo study
,
histopathology
,
in vitro study
,
lipid vesicle
,
male
,
nanoencapsulation
,
nonhuman
,
particle size
,
rat
,
skin permeability
,
zeta potential
Abstract:
Colchicine (CL) is the most effective treatment of acute gout, however, it is associated with side effects in 80% of the patients at therapeutic doses, in addition, it's a water-soluble strong base (pKa ?12.8) which ionizes at physiological gastrointestinal pH resulting in low oral bioavailability of 44%. This work employed enhancing the bioavailability and reducing the side effects of CL through combining the benefits of the transdermal route together with those of elastic lipid nano-vesicles. Transfersomes (TRs) have been studied as vehicles for transdermal drug delivery, however, poor encapsulation of drugs and drug leaking of the vesicles required complexation of CL with ?-cyclodextrin (?-CD) before formulation. The composition of the designed CL-?-CD-TR was studied to balance the flexibility of the vesicles to their entrapment ability. CL-?-CD-TR were characterized for their shape, size, entrapment efficiency, elasticity, release profile, ex vivo skin permeation, pharmacological efficacy, and histopathological effect. Encapsulation efficiency of CL-?-CD complex in the vesicular formulations ranged from 42.3% to 93.8%. Particle size ranged from 70.6 nm to 138.5 nm and zeta potential ranged from 16.1 mV to 23.4 mV. The in vitro release of CL from the selected CL-?-CD-TR formulation (F3) showed a controlled, biphasic profile. Ex vivo study reported the great potential of F3 (CL-?-CD-TR) for skin permeation. In vivo experiment demonstrated that F3 (CL-?-CD-TR) possessed high biological efficacy with reduced skin irritation. � 2018 Elsevier B.V.
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