Novel Siwa propolis and colistin-integrated chitosan nanoparticles: elaboration; in vitro and in vivo appraisal.

Aim: The present study aimed to formulate novel cremophore-decorated chitosan nanoparticles of colistin, integrated with Siwa propolis extract, to solve bacterial resistance to colistin. Materials & methods: The novel nanoformula was prepared using an incorporation method. Physicochemical assessment and in vivo studies of the selected nanoformulations were performed. Results: The nanoformulation exhibited a nanosize of 48.3 nm, high ζ potential (43.6 mV), high entrapment efficiency (75%) and complete bacterial growth eradication within 2 h (minimum inhibitory concentration = 6.25 µg/ml). Histological examination showed that incorporation of colistin into the nanoformulation could successfully prevent its nephrotoxicity. Conclusion: Tailoring of proper nanocarrier could successfully revert bacteria from being colistin-resistant to colistin-sensitive. The developed nanoformulation can be considered as a potential antibacterial agent in pneumonia treatment.

Elaboration of polymersomes versus conventional liposomes for improving oral bioavailability of the anticancer flutamide.

AIM: Flutamide is an outstanding anticancer drug with poor oral bioavailability. This is the first work to investigate the potential of polymersomes versus conventional liposomes to improve flutamide bioavailability. MATERIALS & METHODS: Polymersomes were prepared by solvent-switching technique and successfully optimized with excellent nanometric size (143 nm) and ζ-potential (-33.4 mV). Physicochemical characterization, stability in gastrointestinal tract and in vivo oral pharmacokinetics in male Sprague-Dawely rats were performed. RESULTS: A significantly higher stability in simulated intestinal fluid was demonstrated by polymersomes compared with liposomes. Great improvement in flutamide oral bioavailability in polymersomes compared with both liposomes and drug suspension was obtained. CONCLUSION: Polymersomes are promising nanoplatforms to overcome stability problems of liposomes and to improve flutamide oral bioavailability.

Phytochylomicron as a dual nanocarrier for liver cancer targeting of luteolin: in vitro appraisal and pharmacodynamics.

AIM: A novel luteolin (LUT) loaded dual bionanocarrier 'phytochylomicron' was elaborated to allow LUT injectable delivery and liver cancer targeting. METHODS: LUT-phospholipid complex was prepared and loaded into chylomicron nanocarrier. Then phytochylomicron underwent physicochemical characterization, cell culture and pharmacodynamics studies on a new liver-tumor model. RESULTS: Phytochylomicron showed sustained release pattern with minimum drug leakage until reaching the liver. Cell culture studies showed high growth inhibition of Hep G2 cells with 2.6-fold enhancement in cellular uptake. Pharmacodynamics demonstrated enhanced tumor growth inhibition (sixfold) with a significant tumor size reduction. Finally, cell culture results demonstrated an excellent correlation with pharmacodynamics confirming the obtained findings. CONCLUSION: A novel phytochylomicron nanosystem was successfully elaborated with promising characteristics that promoted injectable LUT delivery and liver cancer targeting. [Formula: see text].

Self-emulsifying preconcentrates of daidzein-phospholipid complex: design, in vitro and in vivo appraisal.

AIM: Self-emulsifying phospholipid-complex preconcentrates (SEPPs) were fabricated to improve oral bioavailability of daidzein (DAI), an anticancer drug with challenging amphiphobic nature and extensive presystemic metabolism. METHODS: DAI-phosphatidylcholine complex was prepared to enhance DAI lipophilicity and loading in SEPPs. The physicochemical characteristics and the pharmacokinetic behavior in rats were studied. RESULTS: Surfactant-free SEPP (plain DAI:Phosal® 53MCT complex) was monodisperse upon aqueous dilution with nanorange globule size (485 ± 15 nm). Compared with drug suspension, it showed enhanced drug release and 2.38-fold enhanced oral bioavailability with minimized drug-induced intestinal irritation. Addition of 30% surfactant/co-surfactant mixture did not show any significant difference in drug release rate or absorption profile. CONCLUSION: The highly safe surfactant-free SEPP could be an effective approach to improve DAI oral bioavailability.

Novel lecithin-integrated liquid crystalline nanogels for enhanced cutaneous targeting of terconazole: development, in vitro and in vivo studies.

Terconazole (Tr) is the first marketed, most active triazole for vaginal candidiasis. Owing to poor skin permeation and challenging physicochemical properties, Tr was not employed for the treatment of cutaneous candidiasis. This is the first study to investigate the relevance of novel lecithin-integrated liquid crystalline nano-organogels (LCGs) to improve physicochemical characteristics of Tr in order to enable its dermal application in skin candidiasis. Ternary phase diagram was constructed using lecithin/capryol 90/water to identify the region of liquid crystalline organogel. The selected organogel possessed promising physicochemical characteristics based on particle size, rheological behavior, pH, loading efficiency, and in vitro antifungal activity. Microstructure of the selected organogel was confirmed by polarized light microscopy and transmission electron microscopy. Ex vivo and in vivo skin permeation studies revealed a significant 4.7- and 2.7-fold increase in the permeability of Tr-loaded LCG when compared to conventional hydrogel. Moreover, acute irritation study indicated safety and compatibility of liquid crystalline organogel to the skin. The in vivo antifungal activity confirmed the superiority of LCG over the conventional hydrogel for the eradication of Candida infection. Overall, lecithin-based liquid crystalline organogel confirmed its potential as an interesting dermal nanocarrier for skin targeting purpose.

Layer-by-layer-coated lyotropic liquid crystalline nanoparticles for active tumor targeting of rapamycin.

AIM: This work spotlights on fabrication of CD44-tropic, layer-by-layer (LbL) coated, liquid crystalline nanoparticles of rapamycin (Rap-LbL-LCNPs) to enhance its water solubility and enable its anticancer use. METHODS: Rap-LCNPs were fabricated using hydrotrope method and then coated using LbL self-assembly technique. RESULTS: LbL coating strategy successfully reduced monoolein-induced hemolysis and increased LCNPs serum stability. Lyophilized Rap-LbL-LCNPs were successfully sterilized using γ-radiations. In CD44-overexpressed MDA-MB-231 cells, Rap-LbL-LCNPs demonstrated superior cytotoxicity compared with the nontargeted formulation. Rap-LbL-LCNPs showed 3.35-fold increase in bioavailability compared with free drug. Rap-LbL-LCNPs significantly inhibited tumor growth, enhanced animal survival and reduced nephrotoxic and hyperglycemic effects of Rap. CONCLUSION: LbL coating strategy of Rap-LCNPs could serve as a promising approach that facilitates Rap use in cancer therapy.

Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies.

Recently, research has progressively highlighted on clues from conventional use of herbal medicines to introduce new anticancer drugs. Aloe-emodin (AE) is a herbal drug with promising anticancer activity. Nevertheless, its clinical utility is handicapped by its low solubility. For the first time, this study aims to the fabrication of surface-functionalized polyethylene glycol liquid crystalline nanoparticles (PEG-LCNPs) of AE to enhance its water solubility and enable its anticancer use. Developed AE-PEG-LCNPs were optimized via particle size and zeta potential measurements. Phase behavior, solid state characteristics, hemocompatibility, and serum stability of LCNPs were assessed. Sterile formulations were developed using various sterilization technologies. Furthermore, the potential of the formulations was investigated using cell culture, pharmacokinetics, biodistribution, and toxicity studies. AE-PEG-LCNPs showed particle size of 190 nm and zeta potential of -49.9, and PEGylation approach reduced the monoolein hemolytic tendency to 3% and increased the serum stability of the nanoparticles. Sterilization of liquid and lyophilized AE-PEG-LCNPs via autoclaving and γ-radiations, respectively, insignificantly affected the physicochemical properties of the nanoparticles. Half maximal inhibitory concentration of AE-PEG-LCNPs was 3.6-fold lower than free AE after 48 hours and their cellular uptake was threefold higher than free AE after 24-hour incubation. AE-PEG-LCNPs presented 5.4-fold increase in t1/2 compared with free AE. Biodistribution and toxicity studies showed reduced AE-PEG-LCNP uptake by reticuloendothelial system organs and good safety profile. PEGylated LCNPs could serve as a promising nanocarrier for efficient delivery of AE to cancerous cells.