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

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.

Nanomedicine, an emerging therapeutic strategy for oral cancer therapy

“…Moreover, NARNPs inhibited tumor proliferation and increased antioxidant levels compared to controls. Gavin et al [47] developed mucoadhesive CS-layered nanoemulsions loaded with genistein (Gen) and processed them into buccal tablet formulations. Cytotoxicity assays on OSCC cell lines revealed significant efficacy of CS-layered Gen-nanoemulsions at early time points compared to aqueous Gen-nanoemulsions [47].…”

“…Gavin et al [47] developed mucoadhesive CS-layered nanoemulsions loaded with genistein (Gen) and processed them into buccal tablet formulations. Cytotoxicity assays on OSCC cell lines revealed significant efficacy of CS-layered Gen-nanoemulsions at early time points compared to aqueous Gen-nanoemulsions [47]. In a more recent study, Li et al [5] evaluated the effect of salvianolic acid B (SalB) phospholipid complex-loaded NPs (SalB-PLC-NPs) on oral pre-cancerous and OSCC cell lines.…”

Transbuccal delivery of betahistine dihydrochloride from mucoadhesive tablets with a unidirectional drug flow: in vitro, ex vivo and in vivo evaluation

“…Adhesion starts to occur after a short time of tablet swelling; however, weak bonds are formed 38. Relaxation of the polymer chains which are present in stretched, twisted or entangled condition occurs as a result of water uptake, leading to exposure of the mucoadhesive sites of the polymer for bonding to occur.…”

New Cellulose-Based Materials as Transdermal Transfer Systems for Bioactive Substances

“…The term bioadhesion is used to describe the attachment of a drug carrier system/formulation to an epithelial tissue due to the action of interfacial forces. 20 The data (Table 2) suggest that the fillers interfere with the ability of the materials to adhere to the substrate. According to Table 2, the cellulose-collagen film presented the highest bioadhesive strength.…”