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Doxorubicin (DOX) is a potent anticancer drug with severe toxic side effects on vital organs. The main mechanism of DOX's toxicity includes overproduction of reactive oxygen species (ROS) causing extensive oxidative stress. In order to minimize DOX-induced hepatotoxicity, cinnamaldehyde (CNM) and naringin (NAR) were co-encapsulated into zein nanoparticles (NPs). Afterwards, the dual-loaded NPs were dual-coated with lactoferrin (LF) and sodium casieate (NaCAS) in order to resist the gastric acidity upon oral administration. CNM/NAR-loaded LF/NaCAS-coated zein NPs exhibited a double coated spherical shape with particle size of 268.5 ± 6.4 nm, zeta potential of −12 ± 1.1 mV, and EE% of 79.54 ± 4.3 for CNM and 73.61 ± 2.9 % for NAR. Moreover, dual drug-loaded LF/NaCAS-coated zein NPs demonstrated slow release of CNM and NAR in simulated gastric fluid (SGF) compared to NaCAS-coated NPs, free CNM and free NAR, resulting in enhanced bioavailability. In addition, the prepared formulation showed good physical stability and hemocompatibility. More importantly, when this formulation was orally administrated to DOX oxidative stress-induced mice, they showed improved liver architecture with reduced inflammation and better antioxidant potential with no signs of toxicity, suggesting a reduction in ROS-mediated damage. In conclusion, CNM/NAR-loaded LF/NaCAS-coated zein NPs might be administrated orally in patients receiving DOX as a natural supplement to reduce the detrimental effects of this potent cytotoxic drug.

Given the great potential of pectin in biomedical applications and the structural advantage of nanoparticles (NPs) embedded in nanofibers (NFs), tadalafil (TDF)-loaded NPs were encapsulated into electrospun pectin/PVA NFs composite in order to afford sustained drug release. TDF-loaded zein/sodium caseinate NPs (zein/Na CAS NPs) were first prepared via anti-solvent method, then the prepared NPs were co-blended with pectin and PVA to obtain the electrospun whole composite. The fabricated composite exhibited proper NFs size and morphology associated with enhanced thermal stability and prolonged drug release for more than 14 days. Furthermore, the prepared composite demonstrated improved in vitrohydrophilic properties that supported cell attachment and growth with a very low hemolytic activity. Furthermore, in vivostudy conducted on a diabetic rat model revealed that the whole composite including TDF-NPs and pectin had superior wound closure, skin regeneration and collagen deposition when compared to pectin/PVA NFs. In addition, the fabricated composite significantly decreased some inflammatory markers (TNF-α, IL-1β and IL-6) in comparison to the untreated diabetic control. In addition, due to TDF's angiogenic properties, the whole composite showed a significant increase in vascular endothelial growth factor (VEGF) protein level. Therefore, this NPs-in-NFs composite approach could serve as an effective diabetic wound dressing.

Background: In the last two decades, the consumption of drugs of abuse among women of childbearing age has experienced a significant increase and results from analyses of surveys concerning maternal intake of psychoactive prescription drugs during pregnancy indicate that the rates of intake are increasing each year. Analyses of biological matrices such as maternal hair and neonatal meconium have recently been used for assessment of gestational consumption and consequent prenatal exposure to drugs of abuse in high-risk groups of women. Methods: Maternal hair and neonatal meconium were analyzed by validated chromatographic-mass spectrometric methodologies to disclose the gestational use of drugs of abuse and psychoactive prescription drugs and consequent prenatal exposure in a cohort of 513 mother-newborn dyads at the Sant Joan de Déu Barcelona Hospital, Spain, during 2012-2013. Results: A total of 3.9% women reported drugs of abuse or prescription psychoactive drug consumption at any time during pregnancy. The prevalence of gestational consumption and the consequent prenatal exposure to drugs of abuse (e.g. cannabis, cocaine and MDMA) was 1.2% in maternal hair and 0.4% in meconium; and of psychoactive prescription drugs (e.g. venlafaxine, citalopram, fluoxetine, clomipramine), was 1.7% in maternal hair and 1.2% in meconium. The prevalence of drugs of abuse and prescription psychoactive drug consumption was lower in our specific cohort of Spanish pregnant women than in other cohorts such as those from U.S. or Denmark. Conclusion: Analysis of materno-fetal matrices provides a viable alternative to study prenatal exposure to these substances and develop specific social and health intervention recommendations.

Background: Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized ‘core–shell’ drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. Method: By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Results: Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Conclusion: Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs.

Breast cancer is the most global dominant cancer among females. Although there are continuously growing strategies to develop new therapies, the outcomes are usually insufficient. Simultaneous combinational therapy using more than one drug is a promising strategy to treat breast cancer. Yet, administration of these drugs in their free form is usually associated with diverse side effects. Nanoencapsulation can afford entrapping drugs within the same nanocarrier for enhanced effect. Protein micelles have been widely utilized in nanoencapsulation owing to their biocompatibility and stability. In this study, dasatinib (DAS) and celecoxib (CXB) were co-encapsulated in the hydrophobic inner core of sodium caseinate micelles via a facile encapsulation method. In vitrocytotoxicity study for the prepared micelles was conducted on MCF-7 (hormone sensitive) and MDA-MB-231 (Triple negative) human breast cancer cell lines to evaluate their anti-cancer effect. Furthermore, the antitumor efficacy and the toxicity of the prepared micelles were examined in breast cancer animal model. Dual drug-loaded micelles revealed improved cytotoxic and synergistic effect against the examined cancer cell lines when compared to free drugs combination. More importantly, in vivostudies demonstrated enhanced antitumor effect with increased apoptosis, reduced angiogenesis, proliferation and migration. In addition, this nanoplatform was found to minimize the cytotoxic effects of both DAS and CXB. In conclusion, utilization of DAS/CXB-loaded sodium caseinate micelles can act as a promising drug delivery platform with increased drugs sensitization and minimized toxicity.

The implementation of naturally available curative compounds or the utilization of green biopolymers especially industrial byproducts, are recently applied to develop new topical formulations for treating or managing skin wounds. In this study, frankincense (FRK) essential oil was extracted from Bosolica papyriferaoliogum resin, and encapsulated into whey protein NPs using spray drying technique. A bionanocomposite film was then prepared by embedding FRK essential oil-loaded whey protein NPs into FRK resin using solvent casting technique. Morphological analysis by TEM showed that the prepared NPs were spherical in shape with diameter of about 151 nm and EE % of about 75.9%. The fabricated film showed good tensile strength and improved sustained release of FRK essential oil compared to the oil-loaded whey protein NPs alone. Moreover, it exhibited a significant antimicrobial behavior with very weak hemolytic activity. More importantly, when this film was applied in a full thickness animal wound model, it displayed remarkably improved healing with enhanced collagen deposition associated with decline in the gene expression of interleukin-6 (IL-6) and an increase in the gene expression of transforming growth factor-β1 (TGF- β1) due to the ability of FRK essential oil to modulate inflammation and skin tissue remodeling, suggesting the excellent feasibility of this film as a highly efficient wound dressing film.