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This study was proposed to develop an optimized sertraline hydrochloride (SER)–loaded bilosomal system and evaluate its potential for enhancement of drug oral bioavailability. A full 23 factorial design was used to prepare SER-loaded bilosomal dispersions by thin film hydration using span 60, cholesterol (CHL), and sodium deoxycholate (SDC). The investigated factors included the total concentration of span 60 and CHL (X1), span 60:CHL molar ratio (X2), and SER:SDC molar ratio (X3). The studied responses were entrapment efficiency (EE%) (Y1), zeta potential (Y2), particle size (Y3), and in vitro % drug released at 2 (Y4), 8 (Y5), and 24 h (Y6). The selected optimal bilosomal dispersion (N1) composition was 0.5% w/v (X1), 1:1 (X2), and 1:2 (X3). Then, N1 was freeze dried into FDN1 that compared with pure SER for in vitro drug release, ex vivo permeation through rabbit intestine, and in vivo absorption in rats. Moreover, storage effect on FDN1 over 3 months was assessed. The optimal dispersion (N1) showed 68 ± 0.7% entrapment efficiency, − 41 ± 0.78 mV zeta potential, and 377 ± 19 nm particle size. The freeze-dried form (FDN1) showed less % drug released in simulated gastric fluids with remarkable sustained SER release up to 24 h compared to pure SER. Moreover, FDN1 showed good stability, fivefold enhancement in SER permeation through rabbit intestine, and 222% bioavailability enhancement in rats’ in vivo absorption study compared to pure SER. The SER-loaded bilosomal system (FDN1) could improve SER oral bioavailability with minimization of gastrointestinal side effects. Graphical abstract

PurposeThis work aimed to synthesize surfactant-free AuNPs for targeted delivery of plasmid DNA encoded p53 gene and to avoid conventional production method of Gold nanoparticles (AuNPs) which may adversely affect the final shape, diversity, and size due to accumulation of the formulated surfactant – gold complex to the surface.MethodsThe AuNPs were fabricated using seeded-growth method with L-Cystine methyl ester hydrochloride as capping agent, then loaded with plasmid DNA encoded p53 gene. The resultant AuNPs and AuNPs-p53 complex were evaluated for physical characteristics and morphology. Confirmation of complex formation was performed using gel electrophoresis. Furthermore, the efficient delivery and cytotoxicity behavior of the encoded gene were examined on both healthy lung cells (WI38) and cancerous lung cells (A549).ResultsL-cysteine methyl ester hydrochloride AuNPs showed acceptable physical characteristics (30 nm, +36.9 mv, and spherical morphology). P53 attachment to AuNPs was confirmed by gel electrophoresis. The RT-PCR proved the overexpression of p53 by the fabricated AuNPs-p53 complex. The high percentage of cell viability in normal lung cell line (WI 38) proved the safety of L-cysteine methyl ester functionalized AuNPs. Additionally, the apoptotic effect due to expression of p53 gene loaded on AuNPs was only prominent in lung cancer cell line (A549), revealing selectivity and targeting efficiency of anticancer AuNPs-p53 complex.ConclusionAuNPs can be considered as a potential delivery system for effective transfection of plasmid DNA which can be used for successful treatment of cancer.

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Background: Thalidomide (THD) and its analogues were recently reported as a promising treatment for different types of solid tumors due to their antiangiogenic effect. Methods: In this work, we synthesized a novel THD analogue (TA), and its chemistry was confirmed with different techniques such as IR, mass spectroscopy, elemental analysis as well as 1 H and 13 C NMR. To increase solubility and anticancer efficacy, a new oil in water (O/W) nanoemulsion (NE) was used in the formulation of the analogue. The novel formula's surface charge, size, stability, FTIR, FE-TEM, in vitro drug release and physical characteristics were investigated. Furthermore, molecular docking studies were conducted to predict the possible binding modes and molecular interactions behind the inhibitory activities of the THD and TA. Results: TA showed a significant cytotoxic activity with IC 50 ranging from 0.326 to 43.26 µmol/mL when evaluated against cancerous cells such as MCF-7, HepG2, Caco-2, LNCaP and RKO cell lines. The loaded analogue showed more potential cytotoxicity against MDA-MB-231 and MCF-7-ADR cell lines with IC 50 values of 0.0293 and 0.0208 nmol/mL, respectively. Moreover, flow cytometry of cell cycle analysis and apoptosis were performed showing a suppression in the expression levels of TGF-β, MCL-1, VEGF, TNF-α, STAT3 and IL-6 in the MDA-MB-231 cell line. Conclusion:The novel NE formula dramatically reduced the anticancer dosage of TA from micromolar efficiency to nanomolar efficiency. This indicates that the synthesized analogue exhibited high potency in the NE formulation and proved its efficacy against triple-negative breast cancer cell line.

Deverra tortuosa (Desf.) DC. and Deverra. triradiata Hochst. ex Bioss are perennial desert shrubs widely used traditionally for many purposes and they are characteristic for their essential oil. The objective of the present study was to investigate the in vivo wound healing activity of the essential oil (EO) of D. tortuosa and D. triradiata through their encapsulation into nanoemulsion. EO nanoemulsion was prepared using an aqueous phase titration method, and nanoemulsion zones were identified through the construction of phase diagrams. The EO was prepared by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and supercritical fluid extraction (SFE) and analyzed using GC/MS. D. tortuosa oil is rich in the non-oxygenated compound, representing 74.54, 73.02, and 41.19% in HD, MADH, and SFE, respectively, and sabinene represents the major monoterpene hydrocarbons. Moreover, D. triradiata is rich in oxygenated compounds being 69.77, 52.87, and 61.69% in HD, MADH, and SFE, respectively, with elemicin and myristicin as major phenylpropanoids. Topical application of the nanoemulsion of D. tortuosa and D. triradiata (1% or 2%) exhibited nearly 100% wound contraction and complete healing at day 16. Moreover, they exhibit significant antioxidant and anti-inflammatory effects and a significant increase in growth factors and hydroxyproline levels. Histopathological examination exhibited complete re-epithelialization accompanied by activated hair follicles and abundant collagen fibers, especially at a concentration of 2%. Therefore, the incorporation of the two Deverra species into nanoemulsion could professionally endorse different stages of wound healing.

Objectives: The aim of this study was to investigate the ability of siRNA-loaded nanoparticles to control the capability of cisplatin-resistant cell lines to decrease cancer metastasis and cell proliferation rate. Methods: The effect of siRNAloaded NPs on the migratory (metastasis) and proliferation (cell growth rate) activity of cisplatin-resistant cell lines compared to untreated cells was investigated using the wound healing assay and cell growth rate assay, respectively. Results:The results showed that cells were treated with siRNA-loaded nanoparticles after 24 h from starting the scratch, succeeded to cover of 59 ± 12.9, and 30 ± 6.1% only from the wound for cell line Cis 1R and Cis 12R, respectively. On the other hand of the untreated cells that were treated with positive control nanoparticles showed complete healing for the wound within the same period of time. Results of cell proliferation of both cell lines exhibited significantly (P≤ 0.001) lower growth rate after treatment with loaded nanoparticles compared to positive control nanoparticles and untreated cells. Conclusion: The obtained results indicated that siRNA-loaded nanoparticles succeeded to not only reduce metastasis but also decrease cell proliferation rate of cisplatin-resistant cell lines.