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Steroids (anti-inflammatory drugs) combined with antioxidants are frequently prescribed to treat cisplatin (CP)-induced hearing loss in the clinic. Compared to systemic administration of free drugs, local drug delivery systems offer better therapeutic qualities and patient compliance since they not only can bypass the blood-labyrinth barrier but also can perform sustained release. In this work, dexamethasone (DEX) and lipoic acid (LA) non-spherical microcrystals (MCs) were prepared without complicated chemical modification. Following a series of physical characterizations, including morphology, stability and injectability, dissolution and round window membrane distribution of MCs, DEX MCs, LA MCs and the simple mixture of DEX MCs + LA MCs (combination group) were administered in guinea pigs by intratympanic injection. We found that LA MCs enabled improvement of DEX absorption in the combination group compared to a single dose. In addition, no significant morphological changes or inflammatory responses were observed in cochlear tissue, indicating good biocompatibility. Finally, the combination group also demonstrated synergistic therapeutic effect for protecting hair cells against CP-induced damage. The local co delivery of DEX MCs and LA MCs offers a new strategy for the treatment of CP-induced inner ear injury since they provide sustained anti-inflammatory and antioxidant effects simultaneously. [Display omitted] • Dexamethasone and lipoic acid non-spherical microcrystals formed by precipitation. • Dexamethasone absorption was increased in the presence of lipoic acid in vivo. • Combined microcrystals provided synergistic therapy for inner ear diseases. [ABSTRACT FROM AUTHOR]

Class IIa bacteriocin pediocin PA-1 has broad-spectrum activity and is a well-characterized candidate food biopreservative. Here, a simple approach is designed to extend the application of pediocin PA-1 in improving the antibacterial activity of electrospun poly(caprolactone) (PCL) grafts through combining PA-1 with HGFI, which is a self-assembled protein with characteristics allowing the modulation of surface properties of other materials originated from Grifola frondosa . Saccharomyces cerevisiae was used as the host for expression of fusion protein PA-1-linker-HGFI (pH) and his-tag purification was used to purify recombinant protein pH. An antibacterial activity assay showed the fusion protein pH retained the biological property of native PA-1. Water contact angle, X-ray photoelectron spectroscopy, immunofluorescence assay and atomic force microscopy indicated the surface properties of HGFI were greatly preserved by the fusion protein pH. Finally, antibacterial activity of pH-modified PCL substrate measurements implied the fusion protein significantly improved the bacterial-resistance of the PCL film through dressing the PCL fibers with the recombinant pH protein. This work presents a new perspective on the application of hydrophobin and pediocin PA-1 in antibacterial medical devices. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The alteration of charged bases influenced the pI value of HGFI. • MGF3 and MGF6 exhibited better surface activity than the wild type HGFI. • Neither MGF3 nor MGF6 have the ability to form rodlets. • Both MGF3 and MGF6 enhanced the stability of IND. • The mutant hydrophobins extended the release time of IND in simulated GI system. Abstract HGFI (hydrophobin found in Grifola frondosa) is a small surface-active protein, belonging to class I hydrophobins, and can form amphipathic protein films at hydrophobic- hydrophilic material interfaces. HGFI has a low isoelectric point (pI) because no basic amino acids are present in its sequence. Here we constructed two HGFI mutants using a site-directed mutation method. The two mutants were named MGF3 (E24K/D35K/D37K) and MGF6 (E12K/D19K/E24K/D35K/D37K/D66K). MGF3 was generated by replacing three acidic amino acids, namely Glu24, Asp35 and Asp37, with the basic amino acid Lys. MGF6 was obtained by substituting Glu12, Asp19, Glu24, Asp35, Asp37 and Asp66 with six Lyses. Zeta-potential analysis showed that the pI values of MGF3 and MGF6 were between 5 and 6. The water contact angle (WCA) and quartz-crystal microbalance (QCM) analyses revealed enhanced adsorption capacity of these two mutants. Circular dichroism measurements (CD), Thioflavin T (THT) assays and atomic force microscopy (AFM) tests indicated that neither MGF3 nor MGF6 have the ability to form rodlets. An in vitro drug release assay showed the water solubility of the indometacin (IND) nano-particles (NPs) was improved by both MGF3 and MGF6 modification. Furthermore, the mutant hydrophobin-modified NPs were more stable and exhibited a lower release rate in solutions at pH 1.2 and 7 at 37 °C. The MGF6-IND NPs showed a particularly improved drug release behavior. These results suggest new applications of the mutated hydrophobins in sustained delivery of oral drugs in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]