β-Caryophyllene-Loaded Microemulsion-Based Topical Hydrogel: A Promising Carrier to Enhance the Analgesic and Anti-Inflammatory Outcomes

Abstract

Musculoskeletal pain and inflammation can vary from localised pain like pain in the shoulders and neck to widespread pain like fibromyalgia, and as per estimates, around 90% of humans have experienced such pain. Oral non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for such conditions but are associated with concerns like gastric irritation and bleeding. In the present study, a microemulsion-based gel comprising β-caryophyllene, isopropyl myristate, Tween 80, and normal saline was prepared as a topical option for managing topical pain and inflammation. The globules of the microemulsion were below 100 nm with a zetapotential of around -10 mV. The drug entrapment was >87% with a drug loading of >23%. The permeation studies established better skin permeation (20.11 ± 0.96 μg cm^-2 h^-1) and retention of the drug (4.96 ± 0.02%) from the developed system vis-à-vis the conventional product (9.73 ± 0.35 μg cm^-2 h^-1; 1.03 ± 0.01%). The dermatokinetic studies established the better pharmacokinetic profile of the bioactive in the epidermis and dermis layers of the skin. The anti-inflammatory potential in carrageenan-induced rat paw oedema was more pronounced than the conventional product (~91% vis-à-vis ~77%), indicating a better pharmacodynamic outcome from the developed system. The nanotechnology-based natural bioactive product with improved efficacy and drug loading can provide a better alternative for the management of musculoskeletal pain.

Keywords: analgesia; bioavailability; dermatokinetics; microemulsion; nanocarrier; safety; skin permeation.

Figure 1

Pseudo-ternary phase diagram constructed between IPM, Smix, and normal saline. Each vertex of the triangle shows 100% of the mentioned component and every circular point shows the boundary between the monophasic and biphasic region.

Figure 2

Transmission electron microphotograph of a frame of the selected microemulsion, i.e., ME2.

Figure 3

Particle size distribution of the developed microemulsion gel.

Figure 4

(A) Rheogram of the hydrogel prepared from the selected microemulsion. (B) The variation of viscosity as a function of shear rate.

Figure 5

Optical microscopy of the developed gel at 1000×.

Figure 6

The graph showing the percent of β-caryophylline permeating across the rodent skin from the tested formulations with respect to time (n = 3). * indicates the significant differences at all the studied time points at p < 0.05.

Figure 7

The graph showing the amount of β-caryophylline per unit area permeating across the (A) epidermis and (B) dermis from the tested formulations with respect to time (n = 3). * indicates the significant differences at all the studied time points at p < 0.05.

Figure 8

The graph showing variation of the % oedema in the paws of rodents receiving various treatments (n = 3). * indicates the significant differences at all the studied time points at p < 0.05.