Phospholipid-Based Topical Nano-Hydrogel of Mangiferin: Enhanced Topical Delivery and Improved Dermatokinetics

Abstract

Mangiferin is a herbal drug that has proven anticancer potential. Owing to its lower aqueous solubility and poor oral bioavailability, the full pharmacological potential of this bioactive drug has not fully been explored. In the present study, phospholipid-based microemulsion systems were developed to bypass oral delivery. The globule size of the developed nanocarriers was less than 150 nm and the drug entrapment was >75% with a drug loading ~25%. The developed system offered a controlled release pattern following the Fickian drug release. This enhanced mangiferin's in vitro anticancer activity by four-fold, the cellular uptake was observed to be improved by three-fold on the MCF-7 cells. Ex vivo dermatokinetic studies showed substantial topical bioavailability with a prolonged residence time. The findings provide a simple technique to administer mangiferin via a topical route promising a safer, topically bioavailable and effective treatment option for breast cancer. Such scalable carriers with immense topical delivery potential may provide a better option for present-day topical products of a conventional nature.

Keywords: anticancer; breast cancer; dermal bioavailability; dermal pharmacokinetics; microemulsion; nanoemulsion; topical administration.

Figure 1

Pseudoternary phase diagram between IPP, water and S_mix (1:1). The red line shows the boundary between the monophasic and biphasic region. The area above redline represents the monophasic region.

Figure 2

Pseudoternary phase diagram between IPP, water and S_mix (2:1). The red line shows the boundary between the monophasic and biphasic region. The area above redline represents the monophasic region.

Figure 3

Pseudoternary phase diagram between IPP, water and S_mix (3:1). The red line shows the boundary between the monophasic and biphasic region. The area above redline represents the monophasic region.

Figure 4

(A): The globule size, polydispersity index and globule size distribution of the formulation F8. (B): The zeta-potential graph of the formulation F8.

Figure 5

The TEM microphotograph of the microemulsion formulation F8.

Figure 6

FT-IR spectrum of: mangiferin (A), microemulsion (B), Labrasol (C), IPP (D) and Gelucire (E).

Figure 6

FT-IR spectrum of: mangiferin (A), microemulsion (B), Labrasol (C), IPP (D) and Gelucire (E).

Figure 7

(A): The graph showing the variation in viscosity and shear stress with the varying values of shear rate for the developed nano-hydrogel. (B): The graph showing the variation in viscosity and shear stress with the varying values of shear rate for the developed conventional gel.

Figure 8

Cumulative drug permeation profiles of mangiferin from the studied systems (n = 3).

Figure 9

Drug retention in the skin from the studied formulations (n = 3).

Figure 10

IC₅₀ values of the tested formulations against MCF-7 cell lines.

Figure 11

Mean plasma mangiferin concentration versus time graph in rodents (n = 4).