Abstract
Borneol as a penetration enhancer is widely used in guiding other components through the biological barrier into the targeting organs or tissues. This study aimed at studying effect and mechanism of synthetic borneol (S-BO) on improving lymphatic-targeting ability of 7-ethyl-10-hydroxycamptothecin liposomes (SN-38-Lips) via increasing lymph node uptake. At first, SN-38-Lips prepared had appropriate particle distribution, drug loading property and compatible stability with S-BO. Both in vitro cellular uptake and in vivo fluorescence imaging showed that 2 and 5 mg/mL S-BO, especially 2 mg/mL S-BO, enhanced cytoplasmic fluorescence signal of SN-38-Lips in the macrophages based on phagocytosis effect. And high-intensity zone appeared in the paracortex and medulla of popliteal lymph node. SN-38-Lips were subcutaneously (s.c.) injected into the right footpad of KM rats in the dose of 4 mg/kg following s.c. injection of 1, 2 and 5 mg/mL BO suspension. The lymphatic pharmacokinetics were investigated to explore the promotion law of S-BO, and combined with tissue irritation to optimize S-BO concentrations. The results indicated that 2 mg/mL S-BO could reduce injection-site retention, and prolong residence time and increase uptake of lymph nodes, which would not cause inflammatory reaction of injection site. In conclusion, the present study may provide a basic study for improving lymphatic-targeting ability of SN-38-Lips by the S-BO regulation, and to be the helpful guidance for further study in lymphatic targeting of delivery system.
Highlights
The lymphatic system as an additional circulatory system, consisting of lymphoid organ, lymph and lymphatic pathways, plays an active role in recognition and response of the immune system to disease (Swartz, 2001)
The results showed that SN-38-Lips as a model drug delivery system had suitable physicochemical properties for in vivo lymphatic uptake study
The particle size (Figure 1(C)) and zeta potential (Figure 1(D)) of SN-38-Lips didn’t showed apparent change when were incubated with synthetic borneol (S-BO) suspension during 12 h
Summary
The lymphatic system as an additional circulatory system, consisting of lymphoid organ, lymph and lymphatic pathways, plays an active role in recognition and response of the immune system to disease (Swartz, 2001). Most solid cancers initially metastasize into the lymph nodes before hematological dissemination (Mcallaster & Cohen, 2011). The lymphatic system has become an important target and drug delivery route for preferential therapeutic and diagnostic agent and improving bioavailability of poorly soluble and unstable drugs that undergo hepatic first-pass metabolism (Singh et al, 2014). The multidisciplinary researchers pay close attention to the improvement of lymphatic targeting (Yang et al, 2015). The lymphatic targeting contains both two processes of lymphatic drainage evaluated by lymphatic penetration and lymphatic retention evaluated by lymph node uptake. The common methods of improving the lymphatic targeting (Moghimi & Moghimi, 2008; Willis et al, 2012) are to adjust interstitial osmotic pressure for increasing lymphatic drainage (Yang et al, 2015) or to increase molecular weight (Cohen et al, 2009), loaded in the drug delivery system for enhancing lymphatic uptake
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