Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

Alexandre CC Vieira,1,* Luíse L Chaves,1,* Marina Pinheiro,1 Domingos Ferreira,2 Bruno Sarmento,3–5 Salette Reis1 1UCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, 3I3S, Inst...

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Autores principales:	Vieira ACC, Chaves LL, Pinheiro M, Ferreira D, Sarmento B, Reis S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Box-behnken design delivery leprosy mannose solid lipid nanoparticles and solubility. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e692be4ead8940099c24f35c22187bb5
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spelling	oai:doaj.org-article:e692be4ead8940099c24f35c22187bb52021-12-02T00:37:16ZDesign and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells1178-2013https://doaj.org/article/e692be4ead8940099c24f35c22187bb52016-06-01T00:00:00Zhttps://www.dovepress.com/design-and-statistical-modeling-of-mannose-decorated-dapsone-containin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alexandre CC Vieira,1,* Luíse L Chaves,1,* Marina Pinheiro,1 Domingos Ferreira,2 Bruno Sarmento,3–5 Salette Reis1 1UCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, 3I3S, Institute for Research and Innovation in Health, 4INEB – Institute of Biomedical Engineering, University of Porto, Porto, 5CESPU, Institute of Research and Advanced Formation in Health Sciences and Technology, University Institute of Health Sciences, Gandra, Portugal *These authors contributed equally to this work Abstract: The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box–Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff’s base formation. The variation of the ZP between uncoated (approximately –30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells. Keywords: Box–Behnken design, leprosy, drug delivery, targeting, oral route, solid lipid nanoparticleVieira ACCChaves LLPinheiro MFerreira DSarmento BReis SDove Medical PressarticleBox-behnken designdeliveryleprosymannosesolid lipid nanoparticles and solubility.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2601-2617 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Box-behnken design delivery leprosy mannose solid lipid nanoparticles and solubility. Medicine (General) R5-920
spellingShingle	Box-behnken design delivery leprosy mannose solid lipid nanoparticles and solubility. Medicine (General) R5-920 Vieira ACC Chaves LL Pinheiro M Ferreira D Sarmento B Reis S Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
description	Alexandre CC Vieira,1,* Luíse L Chaves,1,* Marina Pinheiro,1 Domingos Ferreira,2 Bruno Sarmento,3–5 Salette Reis1 1UCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, 3I3S, Institute for Research and Innovation in Health, 4INEB – Institute of Biomedical Engineering, University of Porto, Porto, 5CESPU, Institute of Research and Advanced Formation in Health Sciences and Technology, University Institute of Health Sciences, Gandra, Portugal *These authors contributed equally to this work Abstract: The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box–Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff’s base formation. The variation of the ZP between uncoated (approximately –30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells. Keywords: Box–Behnken design, leprosy, drug delivery, targeting, oral route, solid lipid nanoparticle
format	article
author	Vieira ACC Chaves LL Pinheiro M Ferreira D Sarmento B Reis S
author_facet	Vieira ACC Chaves LL Pinheiro M Ferreira D Sarmento B Reis S
author_sort	Vieira ACC
title	Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
title_short	Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
title_full	Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
title_fullStr	Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
title_full_unstemmed	Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells
title_sort	design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal m-cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/e692be4ead8940099c24f35c22187bb5
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Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

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