Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

Amy Gavin,1 Jimmy TH Pham,2 Dawei Wang,2 Bill Brownlow,3 Tamer A Elbayoumi3 1College of Dental Medicine, 2Arizona College of Osteopathic Medicine, 3Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ, USA Abstract: Oral cavity and oropharyngea...

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Autores principales:	Gavin A, Pham JTH, Wang D, Brownlow B, Elbayoumi TA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/97560da6415345baa1be0e51cb02f2a4
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spelling	oai:doaj.org-article:97560da6415345baa1be0e51cb02f2a42021-12-02T06:34:33ZLayered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics1178-2013https://doaj.org/article/97560da6415345baa1be0e51cb02f2a42015-02-01T00:00:00Zhttp://www.dovepress.com/layered-nanoemulsions-as-mucoadhesive-buccal-systems-for-controlled-de-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Amy Gavin,1 Jimmy TH Pham,2 Dawei Wang,2 Bill Brownlow,3 Tamer A Elbayoumi3 1College of Dental Medicine, 2Arizona College of Osteopathic Medicine, 3Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ, USA Abstract: Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (-28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. Keywords: isoflavone, genistein, chitosan, squamous cell carcinomasGavin APham JTHWang DBrownlow BElbayoumi TADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1569-1584 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Gavin A Pham JTH Wang D Brownlow B Elbayoumi TA Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
description	Amy Gavin,1 Jimmy TH Pham,2 Dawei Wang,2 Bill Brownlow,3 Tamer A Elbayoumi3 1College of Dental Medicine, 2Arizona College of Osteopathic Medicine, 3Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ, USA Abstract: Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (-28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. Keywords: isoflavone, genistein, chitosan, squamous cell carcinomas
format	article
author	Gavin A Pham JTH Wang D Brownlow B Elbayoumi TA
author_facet	Gavin A Pham JTH Wang D Brownlow B Elbayoumi TA
author_sort	Gavin A
title	Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
title_short	Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
title_full	Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
title_fullStr	Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
title_full_unstemmed	Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
title_sort	layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/97560da6415345baa1be0e51cb02f2a4
work_keys_str_mv	AT gavina layerednanoemulsionsasmucoadhesivebuccalsystemsforcontrolleddeliveryoforalcancertherapeutics AT phamjth layerednanoemulsionsasmucoadhesivebuccalsystemsforcontrolleddeliveryoforalcancertherapeutics AT wangd layerednanoemulsionsasmucoadhesivebuccalsystemsforcontrolleddeliveryoforalcancertherapeutics AT brownlowb layerednanoemulsionsasmucoadhesivebuccalsystemsforcontrolleddeliveryoforalcancertherapeutics AT elbayoumita layerednanoemulsionsasmucoadhesivebuccalsystemsforcontrolleddeliveryoforalcancertherapeutics
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Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

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