Nanomedicine: Nanotechnology, Biology and Medicine
Original ArticleAssessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice
Graphical abstract
After demonstrating the ex vivo performance of lecithin-chitosan NP for enhancing the penetration and dermal accumulation of the poorly soluble drug β-lapachone, the efficacy of the treatment was topically assayed in L. major infected BALB/c mice. Despite the treatment did not influence the parasite burden, it down-regulated IL-1β and COX-2 and reduced the neutrophil infiltrate, thus decreasing the necrosis and size of the skin lesion. Our finding offers a new approach of utility for weakening skin damage in cutaneous leishmaniasis lesions.
Section snippets
Preparation and characterization of β-lapachone nanoparticles
β-LP NP were prepared following the procedure reported by Sonvico et al. with modifications.18 Briefly, chitosan (95/100, 1% w/v) was solubilized in 2% w/v lactic acid whereas β-LP (10 mg/mL) was dissolved in an ethanolic solution of LEC. The organic phase was prepared by mixing LEC:DDAB solutions (60:30 mM, respectively) or LEC:MNL solutions (75:45 mM, respectively) in ethanol:acetone (5:4 v/v). Afterwards, β-LP NP suspensions were obtained by injection of 4 mL of this organic mixture into 4 mL of
Preparation and characterization of β-lapachone nanoparticles
LEC-chitosan NP containing MNL or DDAB were prepared and, particle size (Ø), polydispersity index (PDI), Z-potential and encapsulation efficiency (EE) were determined in order to characterize the NP (Table 1). The mean size of the NP prepared for this study ranged from 317 to 574 nm, showing LEC:DDAB NP smaller sizes than LEC:MNL NP. The Z-potential value was higher for the NP containing DDAB (around 90 mV) than those containing MNL (around 30 mV) but in all cases they were positively charged.
Discussion
Looking for a better CL topical therapy and aiming to explore the goodness of NP skin delivery in CL lesions, in the current study, β-LP was encapsulated in NP containing LEC, a safe and biocompatible excipient widely used in delivery systems, as well as chitosan, an antimicrobial agent with penetration-enhancing properties. Moreover, DDAB and MNL, two different lipids with antimicrobial activity20, 21 and different charge, were also included into the formulations to investigate if they could
Acknowledgements
We would like to thank Laura Guembe (Servicio de Morfología, Centro para la Investigación Médica Aplicada, CIMA), Ainhoa Urbiola and Cristina Ederra (Unidad de Imagen, CIMA) for their excellent technical support with imaging techniques.
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2023, International Journal of PharmaceuticsAnticancer activity of β-Lapachone derivatives on human leukemic cell lines
2022, Chemico-Biological InteractionsCitation Excerpt :Ex DC) Standl and Tabebuia avellanedae, respectively [8]. β-lapachone and its derivatives have been shown interesting biological activities in the last decade, such as: anti-Trypanosoma [9–12], antifungal [13,14], antibacterial [15,16], antiviral [17,18], anti-leishmanial [19], anti-schistosomal [20], and anti-inflammatory [21,22] activities. However, one of the most studied activities of β-lapachone is its anticancer activity against different cancer types such as pancreatic cancer, breast cancer, hepatocellular carcinoma, and leukemias [23–26].
Nanotechnology-aided diagnosis, treatment and prevention of leishmaniasis
2021, International Journal of PharmaceuticsBeta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis
2021, PhytochemistryCitation Excerpt :Moreover, another study also showed that the topical application of β-lapachone was able to increase the number of macrophages, inducing the release of VEGF and EGF in a mouse model of burn wounds and accelerating the process of wound healing (Fu et al., 2011). As reported by Moreno et al. (2015), β-lapachone loaded with lecithin-chitosan nanoparticles was able to treat cutaneous leishmaniosis lesions in mice. Although β-lapachone did not show antileishmanial activity, the nanosystem exhibited anti-inflammatory activity mediating the downregulation of IL-1β and COX-2 and decreasing neutrophil infiltration.
Conflict of interest: The authors declare no conflict of interest.
Funding information: This study has been supported by the FIMA Foundation (Fundación para la Investigación Médica Aplicada) and the Institute of Tropical Health. J.S. received a grant of ADA Foundation (Asociación de Amigos, University of Navarra) and E.M. was awarded by the Ministry of Economy and Competitiveness of the Spanish Government (Subprograma: Torres Quevedo).
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The authors have contributed equally to this work.