Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers

Abstract

Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.

Incorporation of Perillyl Alcohol into Lipid-Based Nanocarriers Enhances the Antiproliferative Activity in Malignant Glioma Cells

“…Recently, Peczek et al reported preparation of PA-loaded nanostructure lipid carriers to enhance drug distribution in the brain. These nanocarriers were prepared using PA as an oily phase, Gelucire ® 43/01 as a solid lipid, and an aqueous phase containing polysorbate 80 and soy lecithin, utilizing the hot homogenization technique [31]. Accordingly, there is a need to develop PA loaded lipid-based nanocarriers utilizing other constituents and techniques to enhance the therapeutic efficacy of PA.…”