Preparation, characterization and pharmacodynamic study on deep second degree burns of total flavonoids composite phospholipids liposome of Oxytropis falcata Bunge

Objective: To further rsearch the biological activity of total flavonoids of Oxytropis falcata Bunge on deep second degree (II°) burns by liposome gel and to elucidate its underlying mechanism.

Methods: The total flavonoids composite phospholipids liposome of Oxytropis falcata Bunge (TFOFB-CPL) was synthesized by thin-film dispersion method and the preparation process was optimized via central composite design. The TFOFB-CPL was then characterized by using particle size, polydispersity indexes (PDIs), zeta potential, encapsulation efficiency (EE) and morphology. Moerover, in vitro transdermal test and in vivo pharmacodynamic study included wound healing rate, hematoxylin-eosin (HE) staning, masson staning, western blotting and RT-PCR.

Results: The investigated TFOFB-CPL had a small particle size (≈70 nm) and PDI of <0.2, which was favorable for the accumulation of drugs in burned skin tissues. The transdermal test showed that the cumulative permeation and permeation rate of the TFOFB-CPL gel were lower than that of the TFOFB-CPL and TFOFB ordinary gel at 24 h, and the former could sustain a steady drug release for a long time with a sustained release effect. The HE and Masson staining test indicated that TFOFB-CPL gel could promote the growth of epidermis, skin appendages, fibrovascular and collagen fibers, and had a certain anti-inflammatory effect. TFOFB-CPL gel could facilitate the wound healing process and accelerate the process of burn injury by regulating the p38 mitogen-activated protein kinase (p38 MAPK) signal transduction pathway and nuclear factor-κB/inhibitory factor-κB (NF-κB/IκB) signal pathway in the western blotting assay. The results of RT-PCR demonstrated that TFOFB-CPL gel could promote neonatal wound in the early stage. The formation of blood vessels facilitated early improvement of blood circulation in burn repair sites and promoted wound healing.

Conclusion: The anti-inflammatory activities of TFOFB is well demonstrated in the treatment of deep II° burns. TFOFB-CPL gel has a sustained-release effect during the treatment of deep II° burns with forming a drug depot in dermis layer. TFOFB-CPL gel induces the significant therapeutic effects on deep II° burns, especially during wound healing by inhibiting the activation of p38 MAPK and the degradeation IκBα.

Keywords: Composite phospholipid liposomes; Deep second degree burns; Liposome gel; Total flavonoids of Oxytropis falcata Bunge; Wound healing; drug depot.