Liposomal Encapsulation of Pine Green Cone Essential Oil: The Influence of the Carrier on the Enhancement of Anti-Inflammatory Activity.

Background/Objectives: This study aimed to investigate the traditionally claimed anti-inflammatory effect of essential oil (EO) derived from pine green cones per se and after encapsulation into liposomes, which is expected to enhance its bioactivity and stability. Methods: The chemical profiling of EO was conducted using GC/GC-MS. The physico-chemical characterization of the liposomal formulation (LEO) included encapsulation efficiency, FTIR spectroscopy, and AFM imaging. Additionally, parameters such as mean particle diameter, polydispersity index, zeta potential, pH, and electrical conductivity were evaluated and reassessed after 30 days and 1 year to determine formulation stability. The in vivo anti-inflammatory effect of the EO and LEO was examined using a carrageenan-induced rat paw edema model. Results: The Pinus halepensis EO contained 14 components, mainly, α-pinene, myrcene, and (E)-caryophyllene. Encapsulation efficiency was 97.35%. AFM analyses confirmed the nanoscale dimensions and spherical shape of liposomes, while FTIR indicated successful encapsulation through overlapping functional groups. The droplet size of blank liposomes (L) ranged from 197.4 to 217 nm, while adding the EO decreased the droplet size and electrical conductivity. The polydispersity index (PDI) remained below 0.2. The zeta potential of the liposomes was between -35.61 and -49.43 mV, while the pH value was in the range of 4.35 to 5.01. These results indicate satisfactory stability across repeated measurements. Administration of LEO significantly inhibited paw edema relative to the controls, with a percentage inhibition of approximately 69%, which does not significantly differ from the effect of hydrocortisone, which was used as a positive control. Conclusions: This is the first study to report liposomal encapsulation and in vivo anti-inflammatory activity of an EO derived specifically from green cones of P. halepensis. Our findings demonstrate that EO-loaded liposomes exhibited favorable physico-chemical properties and notable anti-inflammatory activity, comparable to that of hydrocortisone. These results support their potential application in the development of effective topical anti-inflammatory formulations.