Biomimetic Milk Lipid Nanoparticles Outperform Natural Camel Milk-Derived Exosomes for Enhanced Oral Cannabidiol Delivery

Sandeep Chary Padakanti, PhD
Florida A&M University

Co-authors: Sandeep Chary Padakanti¹, Aakash Nathani¹, Arvind Bagde¹, Mandip Singh Sachdeva^1
1Florida A&M University

Background: Cannabidiol (CBD) has substantial therapeutic potential, but its oral delivery is limited by poor aqueous solubility, variable intestinal absorption, and extensive first-pass metabolism. In our previously published work, camel milk-derived exosomes significantly enhanced the intestinal permeability and oral bioavailability of CBD. Building on this biological platform, we rationally reconstructed camel milk exosomal lipids into biomimetic lipid nanoparticles designed to preserve the membrane-fusion and gastrointestinal transport properties of natural exosomes while overcoming their limitations in drug loading, manufacturing reproducibility, and scalability.

Objectives: To evaluate whether biomimetic camel milk-inspired lipid nanoparticles reconstructed from exosomal lipids could outperform natural camel milk-derived exosomes as an oral CBD delivery platform.

Methods: CBD-loaded camel milk-derived exosomes and biomimetic camel milk lipid nanoparticles were prepared and characterized using various analytical tools. Lipid nanoparticles were formulated from major camel milk exosomal lipids with oral absorption enhancers. CBD incorporation were evaluated using analytical method. In-vitro release, epithelial permeability, release kinetic modeling, and oral pharmacokinetic studies in Sprague-Dawley rats were performed and compared with the previously reported exosome formulation and free-CBD controls.

Results: Camel milk lipid-based nanoparticles demonstrated superior physicochemical and oral delivery performance compared with CBD-loaded camel milk-derived exosomes. The lipid nanoparticles exhibited a smaller particle size of 100.6±0.23 nm, compared with 138.4±4.37 nm for CBD-loaded exosomes, while maintaining a comparable negative surface charge of −42.39±0.51 mV versus −42.07±0.99 mV. CBD entrapment efficiency increased markedly from 56.56±4.26% in the natural exosomes to 87.68±0.51% in the lipid nanoparticles. CBD-loaded exosomes increased apparent permeability to 22.9±0.34 × 10⁻⁶ cm/s, representing a 3.95-fold improvement over free CBD, whereas the lipid nanoparticles produced an even greater permeability response 30.12±0.84 × 10⁻⁶ cm/s. The lipid nanoparticles also provided sustained CBD release over 24 hours, with the Weibull model showing the best overall kinetic fit. In-vivo studies shows, the exosome formulation achieved a Cmax of 448.90±78.53 ng/mL and an AUC₀–₂₄ of 1350.56±187.50 h·ng/mL. The lipid nanoparticle plasma profile showed a higher peak concentration, approximately 651.41±81.23 ng/mL at 4 hours, indicating further improvement in systemic CBD exposure. Thus, rational reconstruction of camel milk exosomal lipids produced a smaller, more drug-efficient nanocarrier with enhanced permeability and greater peak oral absorption than the natural exosome platform.

Conclusion: These findings establish biomimetic milk lipid nanoparticles as a next-generation, scalable oral nanocarrier platform that preserves the biological advantages of natural exosomes while delivering superior formulation performance and enhanced oral bioavailability of cannabinoids and other poorly bioavailable lipophilic therapeutics.