ABSTRACT
@#【Objective】 To develop and optimize niosomal and proniosomal vesicular delivery systems for a naturally occurring polyphenol chlorogenic acid (CGA), so as to improve its physicochemical properties and permeability, which may enhance its pharmacological activity. 【Methods】 The formulated CGA niosomes (CGANs) and CGA proniosomes (CGAPNs) were primed by thin film hydration and phase separation coacervation methods, and were characterized with different attributes including particle size, morphology, entrapment efficiency, zeta potential, deformability, in vitro diffusion, ex vivo permeability, and long-term stability. Their efficiency was further evaluated with in vitro antioxidant assay, antibacterial assays, and excision wound healing model in rats. 【Results】 Optimized CGANs and CGAPNs showed spherical vesicles with particle size of 490.1 ± 43.0 and 280.0 ± 22.0 nm, polydispersity index (PDI) values of 0.526 and 0.173, and stable zeta potential values of - 29.3 ± 6.4 and - 33.2 ± 6.5 mV, respectively. The CGANs and CGAPNs vesicles showed higher entrapment (98.27% ± 0.46% & 97.27% ± 0.25%) with good deformability (8.77 ± 0.22 & 6.87 ± 0.17), higher in vitro diffusion (97.96% ± 1.67% & 91.00% ± 1.32%), and permeability coefficient values (67 ×10-3 ± 1.72 & 52 ×10-3 ± 1.09) with long-term stability in comparison with plain CGA. Enhanced 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and Fe2 + chelation ability was obtained with CGAPNs > CGANs. They also demonstrated lethal bactericidal activity on different gram positive and gram negative strains with lower minimum inhibitory concentration (MIC) values (8 × and 16 × times less) as compared with plain CGA. Significant reduction (P < 0.05) in wound area with higher wound contraction percentages on day 9 was observed with CGANPs (99.56%) > CGANs (98.44%) in comparison with marketed (92.89%) and CGA (88.89%) hydrogel. 【Conclusion】 These results show great potential of CGANs and CGAPNs for topical wound healing application. This is the first study of CGA in niosomal and proniosomal topical delivery systems.
ABSTRACT
Objective: The present research work was designed to formulate and optimize doxorubicin HCl proniosomes by design of experiment (DoE). Methods: A 4-factor, 3-level Box-Behnken design was used to explain multiple linear regression analysis and contour 3D plot responses. The independent variables selected were tween 20, cholesterol, hydration volume and sonication time; dependent variables percentage entrapment efficiency (PEE), mean vesicle size (MVS). Based on the Box-Behnken design 29 trial runs were studied and optimized for PEE and MVS. Further "Model F-Value" was calculated to confirm the omission of insignificant terms from the full-model equation to derive a multiple linear regression analysis to predict the PEE and MVS of niosomes derived from proniosomes. 3D plots were constructed to show the influence of independent variables on dependent variables. Results: PEE of doxorubicin HCl proniosomes was found to be in the range of 40.21-87.5%. The polynomial equation for PEE exhibited a good correlation coefficient (0.5524) and the "Model F-Value" of 7.41 implies the model is significant. P-values less than 0.0500 indicate model terms are significant. The MVS of doxorubicin HCl proniosomes was found to be in the range of 325.2 nm to 420.25 nm. The mathematical model generated for MVS (R2) was found to be significant with model F-value of 54.22. There is only a 0.01% chance that a "Model F-Value" this large could occur due to noise (P<0.0500) and R2 value of 0.9004. Conclusion: The DoE of Box-Behnken design demonstrated the role of the derived equation, 3D plot in predicting the values of dependent variables for the preparation and optimization of doxorubicin HCl proniosomes. The results suggest that doxorubicin HCl proniosomes can act as a promising carrier.
ABSTRACT
Nisoldipine is used for treatment of hypertension and angina pectoris. However, it suffers from very low bioavailability due to its extensive pre-systemic metabolism. This together with its low dose made it excellent candidate for transdermal delivery. Accordingly, the aim of this study was to develop and evaluate transdermal delivery system for optimization of nisoldipine skin permeability. Proniosomes comprising cholesterol and span 60 with different ratios together with ethanol and minimal water were evaluated for such aim. The developed formulations were assessed with respect to drug entrapment efficiency, viscosity, in vitro drug release and transdermal permeability. All proniosomal formulations have significantly enhanced transdermal delivery of nisoldipine compared with saturated aqueous solution of the drug. Increasing cholesterol content resulted in reduced drug flux. The study was extended to compare the efficacy of such proniosomes to the corresponding niosomes. Proniosomes significantly optimized transdermal delivery of nisoldipine compared to their hydrated form. Such results contradict the hypothesis which claimed the necessity for niosome formation from proniosomes for efficient transdermal delivery with penetration enhancement being mainly responsible for improved delivery.
ABSTRACT
The objective of the present study was to formulate and evaluate Tretinoin proniosomal gel and to carry out comparative skin irritation study with conventional Tretinoin solution and Tretinoin conventional gel. Topical Tretinoin (0.25%, 0.05%) has been a reliable treatment of acne vulgaris since 30 years but its major drawback is that it causes skin irritation on the applied area. The proniosomal dispersion was prepared using different grades of non-ionic surfactants and cholesterol in different ratios along with Tretinoin. The scanning electron microscopy revealed that the proniosome vesicles were of LUV type and spherical shape. The proniosome vesicles prepared with SPAN 60, 40 and cholesterol in formulation PN9 showed maximum entrapment efficiency (76.77±1.54) .The prepared proniosome vesicles were incorporated into Carbopol gel (1%) base to prepare Tretinoin proniosomal gel. The stability study was carried out at different accelerated and non-accelerated conditions. The In-vitro diffusion study carried out using sigma dialysis membrane showed sustained release pattern of Tretinoin from proniosomal gel formulation. The comparative skin irritation study carried out on 18 healthy Wistar Rats of either sex showed remarkable decrease in signs of skin irritation caused by Tretinoin.