Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ferreira DS, Faria SD, Lopes SCA, Teixeira CS, Malachias A, Magalhães-Paniago R, de Souza Filho JD, Oliveira BL, Guimarães AR, Caravan P, Ferreira LAM, Alves RJ, Oliveira MC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Hydroxyapatite-targeted formulations bisphosphonates pH-responsive nanostructures bone tumor treatment Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3261c05bd2b542f0b02ed76ddc6c283e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3261c05bd2b542f0b02ed76ddc6c283e
record_format	dspace
spelling	oai:doaj.org-article:3261c05bd2b542f0b02ed76ddc6c283e2021-12-02T05:02:18ZDevelopment of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis1178-2013https://doaj.org/article/3261c05bd2b542f0b02ed76ddc6c283e2016-08-01T00:00:00Zhttps://www.dovepress.com/development-of-a-bone-targeted-ph-sensitive-liposomal-formulation-cont-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira,2 Alexander Ramos Guimarães,2 Peter Caravan,2 Lucas Antônio Miranda Ferreira,1 Ricardo José Alves,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy,Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Physics, 4Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.Purpose: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methods: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals.Results: Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.Conclusion: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity. Keywords: hydroxyapatite-targeted formulations, bisphosphonates, pH-responsive nanostructures, bone-tumor treatmentFerreira DSFaria SDLopes SCATeixeira CSMalachias AMagalhães-Paniago Rde Souza Filho JDOliveira BLGuimarães ARCaravan PFerreira LAMAlves RJOliveira MCDove Medical PressarticleHydroxyapatite-targeted formulationsbisphosphonatespH-responsive nanostructuresbone tumor treatmentMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3737-3751 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hydroxyapatite-targeted formulations bisphosphonates pH-responsive nanostructures bone tumor treatment Medicine (General) R5-920
spellingShingle	Hydroxyapatite-targeted formulations bisphosphonates pH-responsive nanostructures bone tumor treatment Medicine (General) R5-920 Ferreira DS Faria SD Lopes SCA Teixeira CS Malachias A Magalhães-Paniago R de Souza Filho JD Oliveira BL Guimarães AR Caravan P Ferreira LAM Alves RJ Oliveira MC Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
description	Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira,2 Alexander Ramos Guimarães,2 Peter Caravan,2 Lucas Antônio Miranda Ferreira,1 Ricardo José Alves,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy,Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Physics, 4Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.Purpose: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methods: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals.Results: Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.Conclusion: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity. Keywords: hydroxyapatite-targeted formulations, bisphosphonates, pH-responsive nanostructures, bone-tumor treatment
format	article
author	Ferreira DS Faria SD Lopes SCA Teixeira CS Malachias A Magalhães-Paniago R de Souza Filho JD Oliveira BL Guimarães AR Caravan P Ferreira LAM Alves RJ Oliveira MC
author_facet	Ferreira DS Faria SD Lopes SCA Teixeira CS Malachias A Magalhães-Paniago R de Souza Filho JD Oliveira BL Guimarães AR Caravan P Ferreira LAM Alves RJ Oliveira MC
author_sort	Ferreira DS
title	Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
title_short	Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
title_full	Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
title_fullStr	Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
title_full_unstemmed	Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
title_sort	development of a bone-targeted ph-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/3261c05bd2b542f0b02ed76ddc6c283e
work_keys_str_mv	AT ferreirads developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT fariasd developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT lopessca developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT teixeiracs developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT malachiasa developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT magalhatildeespaniagor developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT desouzafilhojd developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT oliveirabl developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT guimaratildeesar developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT caravanp developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT ferreiralam developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT alvesrj developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis AT oliveiramc developmentofabonetargetedphsensitiveliposomalformulationcontainingdoxorubicinphysicochemicalcharacterizationcytotoxicityandbiodistributionevaluationinamousemodelofbonemetastasis
_version_	1718400760245387264

Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

Ejemplares similares