Hydrophobin-nanofibrillated cellulose stabilized emulsions for encapsulation and release of BCS class II drugs

Abstract

The purpose of this study was to construct biopolymer-based oil-in-water emulsion formulations for encapsulation and release of poorly water soluble model compounds naproxen and ibuprofen. Class II hydrophobin protein HFBII from Trichoderma reesei was used as a surfactant to stabilize the oil/water interfaces of the emulsion droplets in the continuous aqueous phase. Nanofibrillated cellulose (NFC) was used as a viscosity modifier to further stabilize the emulsions and encapsulate protein coated oil droplets in NFC fiber network. The potential of both native and oxidized NFC were studied for this purpose. Various emulsion formulations were prepared and the abilities of different formulations to control the drug release rate of naproxen and ibuprofen, used as model compounds, were evaluated. The optimal formulation for sustained drug release consisted of 0.01% of drug, 0.1% HFBII, 0.15% oxidized NFC, 10% soybean oil and 90% water phase. By comparison, the use of native NFC in combination with HFBII resulted in an immediate drug release for both of the compounds. The results indicate that these NFC originated biopolymers are suitable for pharmaceutical emulsion formulations. The native and oxidized NFC grades can be used as emulsion stabilizers in sustained and immediate drug release applications. Furthermore, stabilization of the emulsions was achieved with low concentrations of both HFBII and NFC, which may be an advantage when compared to surfactant concentrations of conventional excipients traditionally used in pharmaceutical emulsion formulations.

Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels

“…The plant derived native nanofibrillar cellulose (NFC) hydrogel, GrowDex®, provides a wellcharacterized and defined matrix [17,25] . This hydrogel is easy to handle and is biocompatible with human cells, whilst also allowing the simple retrieval of cells from the scaffold for further use [25,26]. Although the immunogenicity of plant-derived NFC is still under investigation, the low immune response to other plant derived hydrogels has been reported [27] [12,28].…”

Parenteral nanosuspensions: a brief review from solubility enhancement to more novel and specific applications

“…5 ) prepared with nanoprecipitation method. Till date hydrophobin׳s use as a stabilizing agent is reported only for the topical and oral nanosuspensions, that leaves a lot of room for expanding its horizons for parenteral administration, provided suitable toxicity are generated first 90 , 91 .

Figure 5 TEM images showing beclomethasone dipropionate (BDP) precipitation in deionized water (A) without class II hydrophobin (HFBII), (B) with 0.005% HFBII, (C) with 0.05% HFBII, and (D) with 0.1% HFBII (Scale bar: 0.5 µm).

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Hydrophobins: multifunctional biosurfactants for interface engineering

“…Given their high surface activity, hydrophobin-based drug stabilization has been an area of active research [37–42]. Valo et al demonstrated the preparation of class II hydrophobin-coated drug nanoparticles below 200 nm that were stable for at least 5 h in suspension, and for longer times after freeze-drying [37].…”

“…They showed that the formulation was biocompatible and exhibited a high drug loading, high nanoparticle yield, small particles of narrow distribution, and delayed drug release in rats [41]. Moreover, the effective stabilization of model drug oil-in-water emulsions using low concentrations of HFBII with nanofibrillar cellulose suggests an additional advantage of formulation with hydrophobins since less material is needed compared to traditional pharmaceutical surfactant-based emulsion stabilizers [42]. When the class I hydrophobin SC3 was used to solubilize the hydrophobic drugs cyclosporine A and nifedipine, the oral bioavailability was increased by 2- and 6-fold, respectively [44].…”