Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their superior properties viz: biocompatibility, minute size, inert core, and tunable surface chemistry. The use of NDs for the delivery of anticancer drugs has been at the forefront of NDs applications owing to their ability to increase chemosensitivity, sustain drug release, and minimize drug side effects. Accelerated steps towards the move of NDs from bench side to bedside have been recently witnessed. In this review, the effects of NDs production and purification techniques on NDs' final properties are discussed. Special concern is given to studies focusing on NDs use for anticancer drug delivery, stability enhancement and mediated targeted delivery. The aim of this review is to put the results of studies oriented towards NDs-mediated anticancer drug delivery side by side such that the reader can assess the potential use of NDs in clinics and follow up the upcoming results of clinical testing of NDs on animals and humans.

OBJECTIVES: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK).

SIGNIFICANCE: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers.

METHODS: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits.

RESULTS: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75 ± 0.64 to 498.95 ± 0.64 nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96-77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN and Ketoroline).

CONCLUSIONS: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.

Ischemic stroke is a major cause of death and motor disabilities all over the world. It is a muti-factorial disorder associated with inflammatory, apoptotic, and oxidative responses. Nateglinide (NAT), an insulinotropic agent used for the treatment of type 2 diabetes mellitus, recently showed potential anti-inflammatory and anti-apoptotic effects. The aim of our study was to elucidate the unique neuroprotective role of NAT in the middle cerebral artery occlusion (MCAO)-induced stroke in rats. Fifty-six male rats were divided to 4 groups (n = 14 in each group): the sham-operated group, sham receiving NAT (50 mg/kg/day, p.o) group, ischemia/reperfusion (IR) group, and IR receiving NAT group (50 mg/kg/day, p.o). MCAO caused potent deficits in motor and behavioral functions of the rats. Significant increase in inflammatory and apoptotic biomarkers has been observed in rats' hippocampi. Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was significantly stimulated causing activation of series inflammatory biomarkers ending up neuro-inflammatory milieu. Pretreatment with NAT preserved rats' normal behavioral and motor functions. Moreover, NAT opposed the expression of hypoxia-inducible factor-1α (HIF-1α) resulting in downregulation of more inflammatory mediators namely, NF-κB, tumor necrosis factor-β (TNF-β), and the anti-survival gene PMAIP-1. NAT stimulated caveolin-1 (Cav-1) which prevented expression of oxidative biomarkers, nitric oxide (NO), and myeloperoxidase (MPO) and hamper the activation of apoptotic biomarker caspase-3. In conclusion, our work postulated that NAT exhibited its neuroprotective effects in rats with ischemic stroke via attenuation of different unique oxidative, apoptotic, and inflammatory pathways.