Capsaicin Loaded Solid SNEDDS for Enhanced Bioavailability and Anticancer Activity: In-Vitro, In-Silico, and In-Vivo...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Capsaicin, a natural compound, has therapeutic potential but suffers from poor oral bioavailability.
• Developing effective oral delivery systems is crucial for maximizing capsaicin's therapeutic benefits.

Purpose of the Study:

• To fabricate and characterize capsaicin-loaded self-nanoemulsifying drug delivery systems (SNEDDS) for improved oral administration.
• To evaluate the in vitro and in vivo performance of the developed SNEDDS, including drug release, anti-cancer efficacy, and bioavailability.

Main Methods:

• Construction of pseudo-ternary phase diagrams to identify optimal SNEDDS components (isopropyl myristate, Labrafil, ethanol).
• Formulation and characterization of liquid and solid SNEDDS (S-SNEDDS) using neusilin® US2.
• In vitro drug release studies, Fourier-transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), Transmission electron microscopy (TEM), cell proliferation assays (HT-29 cells), and apoptosis assays.

Main Results:

• The optimized S-CAP-3 formulation exhibited high transmittance and rapid self-emulsification.
• FT-IR, DSC, and XRD confirmed the absence of drug-excipient incompatibility and revealed the amorphization and molecular dispersion of capsaicin.
• TEM confirmed the formation of nano-sized spherical globules.
• S-SNEDDS demonstrated significantly enhanced in vitro drug release (85.19%) compared to pure capsaicin (16.61%).
• S-CAP-3 significantly inhibited HT-29 colorectal cancer cell proliferation and induced apoptosis.
• A remarkable 3.6-fold increase in oral bioavailability of capsaicin was observed with the SNEDDS formulation.

Conclusions:

• Capsaicin-loaded SNEDDS represent a promising oral drug delivery system for enhancing capsaicin's therapeutic efficacy.
• The developed S-SNEDDS formulation shows significant potential for anti-cancer applications due to improved bioavailability and direct cytotoxic effects.