Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs

Abstract

Background:The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug -bovine serum albumin (BSA) -to improve drug stability. Methods: The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity. Results: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (.90%) and an adequate drugloading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA. Conclusions: BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs. Keywords: nanoemulsion, drug-delivery system, protein drug, oral administration, stability IntroductionMany protein targets and protein drugs have recently been discovered, with approximately a dozen therapeutic protein drugs receiving regulatory approval each year around the world.1,2 Over 125 protein drugs are already in the US market, and the value of advanced drug-delivery systems in this market had reached $121 billion by 2010.3 Although many varieties of protein drugs have been designed for therapeutic purposes, several challenges remain, including enzymatic susceptibility, stability during storage period, and efficacy after administration. 4 Thus, protein stability is one of the major hurdles for a drug's successful entry into the market. 5 At present, many of the marketed protein drugs are mainly designed for injective delivery. Because of the thermal instability of protein drugs, they need to be stored and transported at cold temperatures in order to ensure long shelf life. 5,6Dovepress submit your manuscript | www.dovepress.com To overcome the crucial problem of protein instability, stabilizers such as nonionic surfactants, cyclodextrin derivatives, poloxamers, glycerol, ethylene glycol, glucose, sucrose, and trehalose have been used. 7 However, the effects of these stabilizers vary among different proteins. With a view to en...

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