Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies

Abstract

Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and good safety. They are promising vehicles for topical drug delivery. This study aims to increase the skin distribution of podophyllotoxin (POD) by incorporating it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)-POD-NLC formulation 1 and POD-NLC formulation 2 -were prepared and characterized. Their skin targeting efficiencies were compared by conducting in vitro and in vivo experiments. Obviously smaller mean particle size was observed for POD-NLC formulation 1 (106 nm) than POD-NLC formulation 2 (219 nm), whereas relatively low POD loadings (less than 0.5%) were observed for both POD-NLC formulation 1 (0.33%) and POD-NLC formulation 2 (0.49%). Significantly higher in vitro and in vivo rat skin deposit amounts of POD (p < 0.01) were detected after the topical application of POD-NLC formulation 1 compared to POD-NLC formulation 2 . To visualize the skin distribution behavior of hydrophobic active pharmaceutical ingredients (APIs) when NLCs were used as carriers, POD was replaced with Nile red (NR-a hydrophobic fluorescent probe), and the distribution behavior of NR-NLC formulation 1 and NR-NLC formulation 2 in rat skin in vivo was observed using confocal laser scanning microscopy (CLSM). Higher fluorescent intensity was observed in rat skin after the topical application of NR-NLC formulation 1 than NR-NLC formulation 2 , suggesting that higher skin targeting efficiency might be obtained when NLCs with smaller mean particle size were used as carriers for hydrophobic APIs. This result was in accordance with those of skin distribution evaluation experiments of POD-NLCs. Skin irritation property of POD-NLC formulation 1 was investigated and no irritation was observed in intact or damaged rabbit skin, suggesting it is safe for topical use. Our results validated the safety of NLCs when applied topically. More importantly, mean particle size might be an important parameter for formulation optimization when NLCs are used as carriers for hydrophobic APIs for topical application, considering that their loading is relatively low.

Development of podophyllotoxin‑loaded nanostructured lipid carriers for the treatment of condyloma acuminatum

“…Nanoparticles with mucoadhesive properties have previously been used to facilitate drug administration to the mucosa and improve the active effects of transmucosal administration ( 31 ). In the present study, in vitro experimentation indicated that the residence time of POD-NLCs was increased compared with POD-T. POD-NLCs enable sustained drug delivery for 60 h, consistent with results of a previous study, which used POD-NLCs for targeted drug delivery ( 12 ). In the present study, the in vivo drug release from POD-NLCs in Tibetan miniature pigs was monitored by detecting the amount of POD in the cervical mucus and mucosal tissue.…”

“…A previous study reported that NDCs improve the physical and chemical properties of drugs, provide sustained, targeted release and reduce systemic absorption ( 10 ). Nanostructured lipid carriers (NLCs) are a novel type of NDC developed from solid lipid nanoparticles, in which a solid matrix is blended with a fluid lipid to improve drug loading capacity and release properties ( 10 – 12 ). NLCs are able to adhere to the skin surface and transport drugs in a controlled manner, while causing minimal irritation ( 13 ).…”

Nanostructured Lipid Carriers: A Groundbreaking Approach for Transdermal Drug Delivery

“…The motion of the hair may likewise add to the penetration of nanoparticles of a size of 20 nm. 97 Lipids that resemble the composition of sebum may likewise advance follicular penetration as a high sebum/water partition coefficient is a basic characteristic for transport into HF. Epidermal targeting may also be assumed due to a dissolution or erosion of…”

Successful treatment of refractory genital warts using 0.5% podophyllotoxin‐loaded nanostructured lipid carriers

“…Nanostructured lipid carriers (NLC), a novel type of delivery system, exhibit high skin targeting efficiency and good safety (Zhao et al, 2016). Compared with traditional POD tincture, POD-NLC was able to adhere to the skin surface and transport POD in a mild and controlled manner, minimizing irritation and toxicity (Zhao et al, 2016;Gao et al, 2018). To date, there is no evidence showing any therapy is superior to another, nor is any strategy suitable for all patients with genital warts.…”