Optimization of hyaluronan-enriched cubosomes for bromfenac delivery enhancing corneal permeation: characterization, ex vivo, and in vivo evaluation.

To design and evaluate hyaluronan-based cubosomes loaded with bromfenac sodium (BS) for ocular application to enhance the corneal permeation and retention in pterygium and cataract treatment. BS-loaded cubosomes were prepared by the emulsification method, employing 23 full factorial design using Design-Expert® software. Glycerol monoolein (GMO) and poloxamer 407 (P407) as lipid phase and polyvinyl alcohol (PVA) as stabilizer were the used ingredients. The optimized formulation (OBC; containing GMO (7% w/w), P407 (0.7% w/w) and PVA (2.5% w/w)) was further evaluated. OBC had an entrapment efficiency of 61.66 ± 1.01%, a zeta potential of -30.80 ± 0.61 mV, a mean particle size of 149.30 ± 15.24 nm and a polydispersity index of 0.21 ± 0.02. Transmission electron microscopy confirmed its cubic shape and excellent dispersibility. OBC exhibited high stability and no ocular irritation that was ensured by histopathology. Ex vivo permeation study showed a significant increase in drug deposition and permeability parameters through goat cornea, besides, confocal laser microscopy established the superior permeation capability of OBC, as compared to drug solution. In vivo pharmacokinetics in aqueous humor indicated higher AUC0-tlast (18.88 µg.h/mL) and mean residence time (3.16 h) of OBC when compared to the marketed eye drops (7.93 µg.h/mL and 1.97 h, respectively). Accordingly, hyaluronan-enriched cubosomes can be regarded as a promising carrier for safe and effective topical ocular delivery.

New phthalimide analog ameliorates CCl4 induced hepatic injury in mice via reducing ROS formation, inflammation, and apoptosis.

The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.

Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats.

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that Cmax and AUC0-6 h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.