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Nanoparticles-in-nanofibers composites comprise an attractive approach for controlling release and delivery of many active molecules for versatile biomedical applications. Incorporation of drug-loaded nanoparticles within these composites can afford the encapsulation of one or more drug with sequential drug release, which can be tuned according to the assigned function. Moreover, existence of nanoparticles within the nanofibrous matrix was found to favor the morphological and mechanical properties of the developed composites. In this review, the latest biomedical advances for nanoparticles-in-nanofibers composites will be highlighted including; tissue regeneration, antimicrobial applications, wound healing, cancer management, cardiovascular disorders, ophthalmic applications, vaginal drug delivery, biosensors and biomedical filters. These composites incorporating multiple types of nanoparticles could be very promising drug delivery platforms. [Display omitted] • Nanoparticles-in-nanofibers composites can enhance sustained release of encapsulated drug(s). • Existence of nanoparticles within the nanofibrous matrix can improve properties of these composites. • These composites can be used to fabricate biomaterials with biomedical potentials. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine. Unlabelled Image [ABSTRACT FROM AUTHOR]

Spheroidal microparticles versatility as a drug carrier makes it a real workhorse in drug delivery applications. Despite of their long history, few research publications emphasize on how to improve their potential targeting ability, production rate, and dissolution characteristics. The current research presents an example of the combined state of the art of nano- and microparticles development technologies. Here in a novel on-chip, microfluidics approach is developed for encapsulating amphiphilic nanomicelles–in–sodium alginate spheroid. The designed nano-in-micro drug delivery system revealed a superior cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231), besides, a more sustained release of the drug. Hydrodynamics of the designed microchip was also investigated as a function of different flow rates with an insight on the dimensionless numbers; capillary number and Weber number throughout the microchannels. Our study confirmed the efficient encapsulation of nanomicelles within the alginate shell. The current microfluidics approach can be efficiently applied for uniform production of nano-in-microparticles with potential anticancer capability. [ABSTRACT FROM AUTHOR]

Abstract Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe 3 O 4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g−1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure. Objectives: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy. Methods: We recruited 104 men (17–20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status. Results: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment. Conclusions: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy. [ABSTRACT FROM AUTHOR]

Maternal exposure to tobacco and alcohol is a known cause, among others, for fetal growth restriction (FGR). Clinically, FGR can be subclassified into two forms: intrauterine growth restriction (IUGR) and small for gestational age (SGA), based on the severity of the growth retardation, and abnormal uterine artery Doppler or cerebro-placental ratio. This study aimed at investigating any differential correlation between maternal exposures to these toxins with the two clinical forms of FGR. Therefore, a case-control study was conducted in Barcelona, Spain. Sixty-four FGR subjects, who were further subclassified into IUGR (n = 36) and SGA (n = 28), and 89 subjects matched appropriate-for-gestational age (AGA), were included. The levels of nicotine (NIC) and ethyl glucuronide (EtG), biomarkers of tobacco and alcohol exposure, respectively, were assessed in the maternal hair in the third trimester. Our analysis showed 65% of the pregnant women consumed alcohol, 25% smoked, and 19% did both. The odds ratios (ORs) of IUGR were 21 times versus 14 times for being SGA with maternal heavy smoking, while with alcohol consumption the ORs for IUGR were 22 times versus 37 times for the SGA group. The differential correlations between these toxins with the two subtypes of FGR suggest different mechanisms influencing fetal weight. Our alarming data of alcohol consumption during pregnancy should be considered for further confirmation among Spanish women. [ABSTRACT FROM AUTHOR]

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy. [ABSTRACT FROM AUTHOR]

Background: Prenatal heavy metals exposure has shown a negative impact on birth weight. However, their influence on different clinical forms of fetal smallness was never assessed. Objectives: To investigate whether there is a differential association between heavy metals exposure and fetal smallness subclassification into intrauterine growth restriction (IUGR) and small-for-gestational age (SGA). Method: In this prospective case-control study, we included 178 mother–infant pairs; 96 of appropriate for gestational age (AGA) and 82 of small fetuses diagnosed in third trimester. The small ones were further subclassified into IUGR, n = 49 and SGA, n = 33. Cadmium (Cd), mercury (Hg), lead (Pb), arsenic (As) and zinc (Zn) levels were measured in the maternal and cord serum, and in the placentas of the three groups. Results: Maternal serum level of Cd (p<0.001) was higher in the small fetuses compared to AGA. Fetal serum level of Cd (p<0.001) was increased in the small fetuses compared to AGA. Fetal serum level of Hg (p<0.05) showed an increase in SGA compared to both IUGR and AGA. Fetal serum level of Zn was increased in the AGA (p < 0.001) compared to each of the small fetuses groups. Only differences in the levels between the small fetuses’ subgroups were detected in the fetal serum levels of Cd and Hg. Fetal birth weight was negatively correlated with the fetal serum level of Cd (p < 0.001). No differences in the placental heavy metal levels were observed among the groups. Conclusion: Fetal serum levels of Cd showed differential correlation between small fetuses' clinical subclassification, which together with the increased Cd levels in both maternal and fetal serum of the small fetuses reinforce the negative influence of heavy metals on birth weight. These findings provide more opportunities to verify the role of heavy metals exposure in relation to small fetuses’ subclassification. [ABSTRACT FROM AUTHOR]

Perinatal maternal smoking exposure (PMSE) is one of the major environmental risk factors encountered by the fetus. PMSE is usually associated with adverse pregnancy outcomes that may manifest at different stages of life. Nevertheless, fetal growth restriction is the most common smoking-induced side effect. PMSE induces changes in the maternal multiple organ systems. These alterations may affect placentation, which subsequently affects fetal growth. It is worthy to note, however, that the extent of maternal smoking-induced changes depends mainly on the maternal level of susceptibility. Hence, the perinatal pregnancy outcomes vary depending on the interaction between the triad: the maternal, fetal, and placental modifications, making it more complex. In this review, we try to unveil the effect of smoking-induced maternal changes on the maternal immune, endocrine, and metabolic pathways and their impact on fetal growth. [ABSTRACT FROM AUTHOR]

Nanofibers provide multiple merits for the delivery of many therapeutic agents with versatile biomedical applications. With the fast recent advancement in nanotechnology, nanofibers could be easily fabricated with tunable morphologies and release profiles. Here, we review the most recent approaches in the fabrication of electrospun nanofibers incorporating some natural ingredients for their wound healing potential. In addition, electrospun nanofibers for treatment of skin carcinoma and delivery of different growth factors for tissue regeneration will also be highlighted in this review. Nanofibers incorporating different active therapeutical agents are very promising drug delivery platforms. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background. The cause of secondary amenorrhea in the following case cannot be explained by traditional etiologies. We therefore questioned whether long-term methotrexate treatment played a role as an endometrial inhibitor. Case. A 44-year-old G4P2, with a 5-year history of rheumatoid arthritis, presented with a 2-year history of secondary amenorrhea. The patient took methotrexate since diagnosis. Her FSH, estrogen, prolactin, TSH and T4 levels were normal, her B-HCG was negative, her BMI was 22 and she had no history of Asherman's syndrome. Conclusion. There is no information, based on our search, on whether long-term methotrexate treatment has an effect on the menstrual cycle. This case highlights the need for the elucidation of the effects of long-term methotrexate treatment on the menstrual cycle in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Nowadays, breast cancer is considered one of the most upsetting malignancies among females. Encapsulation of celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles (NPs) produce homogenous and spherical nanoparticles with good encapsulation efficiencies (EE %) and bioavailability. In vitro cytotoxicity study conducted on human breast cancer MDA-MB-231 cell lines revealed that there was a significant decline in the IC50 for encapsulated drugs when compared to each drug alone or their free combination. In addition, results demonstrated that there is a synergism between CXB and PDG as their combination indices were 0.62251 and 0.15493, respectively. Moreover, results of scratch wound healing assay revealed enhanced antimigratory effect of free drugs and fabricated NPs in comparison to untreated cells. Furthermore, In vitro results manifested that formulated nanoparticles exhibited induction of apoptosis associated with reduced angiogenesis, proliferation, and inflammation. In conclusion, nanoencapsulation of multiple drugs into nanoparticles might be a promising approach to develop new therapies for the managing of triple negative breast cancer. [ABSTRACT FROM AUTHOR]

This study aimed to objectively verify smoking and drinking behavior during pregnancy and to disclose self-misreporting through maternal hair analysis. A total of 153 women attending a university hospital in Barcelona (Spain) were selected and interviewed after delivery, on their smoking and drinking habits during pregnancy. A 9-cm hair strand was collected and analyzed by liquid chromatography tandem mass spectrometry for the presence of nicotine (NIC) and ethyl glucuronide (EtG) as biomarkers of tobacco and alcohol consumption, respectively. Concentrations of EtG <7 pg/mg hair and ≥30 pg/mg hair in the 0-3-cm hair segment have been used to assess, respectively, total abstinence and chronic excessive consumption in the previous 3 months, with repetitive moderate drinking lying in the interval 7-30 pg EtG per mg hair. Hair NIC less than 1 ng/mg hair indicates non-exposure to tobacco smoke while hair NIC indicates daily active smoking. In the interview, 28.1% of women declared to have smoked occasionally during gestation, while only 2.6% stated to have consumed alcohol on more than one occasion during pregnancy. Hair testing of smoking biomarkers disclosed that 7.2% of women remained active smokers during the whole pregnancy (hair NIC: 3.21-56.98 ng/mg hair), 16.3% were passive non-smokers or occasional smokers (hair NIC: 1.04-2.99 ng/mg hair), while 76.5% were not exposed to any cigarette smoke (hair NIC < limit of quantification - 0.91 ng/mg hair). Conversely, alcohol hair biomarkers showed that only 35.3% of women were totally abstinent during gestation (hair EtG: 3.89-6.73 pg/mg hair), while 62.7% drank a non-negligible amount of alcohol during pregnancy (hair EtG: 7.06-26.57 pg/mg hair), and 2% were chronic excessive drinkers (hair EtG: 35.33-47.52 pg/mg hair). Maternal hair analysis has shown to be significantly more sensitive than interviews in revealing an alarming misreported prevalence of alcohol use during pregnancy. These findings stress the need to use objective measures to assess alcohol exposure and to consider the inclusion of targeted actions to reduce alcohol consumption in maternal-child health policies. [ABSTRACT FROM AUTHOR]

Quantum dots (QDs) possess characteristic chemical and optical features. In this light, ZnS QDs capped with glutathione (GSH) were synthesized via an easy aqueous co-precipitation technique. Fabricated QDs were characterized in terms of X-ray diffraction (XRD), high resolution transmission electron microscope (HRTEM), Fourier transform infrared (FTIR) and Zeta potential analyses. Optical properties were examined using photoluminescence (PL) and ultraviolet–visible (UV–visible) spectroscopies. Moreover, GSH-capped ZnS QDs were evaluated as an optical probe for non-enzymatic detection of urea depending on the quenching of PL intensity of ZnS QDs in the presence of urea from concentration range of 0.5–5 mM with a correlation coefficient (R2) of 0.995, sensitivity of 0.0875 mM−1 and LOD of 0.426 mM. Furthermore, GSH-capped ZnS QDs-urease conjugate was utilized as an optical probe for enzymatic detection of urea in the range from 1.0 µM to 5.0 mM. Interestingly, it was observed that urea has a good affinity towards ZnS QDs-urease conjugate with a linear relationship between the change of PL intensity and urea concentration. It was found that R2 is 0.997 with a sensitivity of 0.042 mM−1 for mM concentration (0.5–5 mM) and LOD of 0.401 mM. In case of µM concentration range (1–100 µM), R2 was 0.971 with a sensitivity of 0.0024 µM−1 and LOD of 0.687 µM. These data suggest that enzyme conjugation to capped QDs might improve their sensitivity and applicability. [ABSTRACT FROM AUTHOR]

Objective: To determine the proportion of patients diagnosed with cervical cancer or cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3) despite testing negative for HPV.Methods: A prospective study was conducted at a university hospital in Barcelona, Spain, between March 2003 and January 2015 among women with abnormal cytology results according to the Bethesda classification system. All participants underwent HPV testing, cytology, and colposcopy.Results: Among 1376 participants, 609 (44.3%) were diagnosed with CIN 2/3. Of these women, 74 (12.2%) tested negative for HPV. Among 479 women with colposcopy-guided biopsy sampling showing CIN 2/3, cone biopsy results that were negative for CIN 2/3 were more frequent among patients with negative HPV testing (13/61 [21.3%]) than among those with positive HPV tests (58/418 [13.9%]; P=0.03). Additionally, among 59 patients diagnosed with cervical cancer, 9 (15.3%) tested negative for HPV.Conclusion: The HPV test was negative for 12% and 15% of patients diagnosed with biopsy-proven CIN 2/3 and cervical cancer, respectively. [ABSTRACT FROM AUTHOR]

Wound healing is a complicated cellular process with overlapping phases. Naringin (NAR); a flavanone glycoside, possesses numerous pharmacological effects such as anti-inflammatory, antioxidant and anti-apoptotic effects. In the current study, Arabic gum (AG)/pectin hydrogel was utilized to encapsulate NAR. Drug-loaded AG/pectin hydrogel exhibited excellent EE% of about 99.88 ± 0.096 and high DL% of about 16.64 ± 0.013. The formulated drug-loaded hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Zetasizer analyzer, besides determination of equilibrium degree of swelling (EDS%). Afterwards, wound healing potential of NAR-loaded AG/pectin hydrogel was evaluated in an in vivo animal model. Results manifested that NAR-loaded AG/pectin hydrogel was able to accelerate wound healing in terms of enhanced angiogenesis, re-epithelialization and collagen deposition. Furthermore, it significantly (P < 0.001) down-regulated the mRNA expression of inflammatory mediators (TNF-α) and apoptosis (BAX). In addition, NAR-loaded AG/pectin hydrogel was found to possess potent antioxidant activity as it enhanced the levels of SOD and GSH, besides decreasing the levels of MPO, MDA and nitrite. These data suggest that NAR-loaded AG/pectin hydrogel could be utilized in wound healing applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is neurological disorder characterized by dementia which causes severe problems with behavior, thinking and memory. Systemic administration of therapeutics to the central nervous system (CNS) is usually associated with very low efficiency due to presence of blood brain barrier (BBB), which only allows permeation of few types of molecules from the circulation to the CNS. As an alternative, naturally amphiphilic micelles can be utilized to enhance targeted drug delivery to the brain. In this sense, lactoferrin (LF) was covalently attached to conjugated linoleic acid (CLA) via carbodiimide coupling reaction to form a new micellar nanoplatform with particle size of about 53 nm. Afterwards, fabricated micelles were further loaded once again with CLA to enhance its delivery to the CNS. In vitro drug release study revealed that CLA exhibited sustained release at pH 6.8, associated with good hemocompatibility without any remarkable in vivo toxicity in terms of liver and kidney functions. Moreover, in vivo studies showed that the fabricated micelles manifested enhanced in vivo biodistrbution in brain tissue due to the active targeting potential of LF. Additionally, drug-loaded LF-CLA micelles exhibited enhanced cognitive capabilities, reduced brain oxidative stress, inflammation, apoptosis and acetylcholine esterase activity, besides a decline in the deposition of amyloid β peptide1–42 in aluminum chloride Alzheimer's-induced animal model. CLA-based micelles could be a promising CNS actively targeted delivery system with a sophisticated potential to reduce AD symptoms. Unlabelled Image • Conjugation between lactoferrin (LF) and conjugated linoleic acid (CLS) was conducted via carbodiimide coupling reaction. • LF-CLA micelles showed enhanced active targeting potential to brain tissue. • LF-CLA micelles reduced oxidative stress in brain tissue. • LF-CLA micelles reduced inflammation and apoptosis in brain tissue. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium with adaptive metabolic abilities. It can cause hospital-acquired infections with significant mortality rates, particularly in people with already existing medical conditions. Its ability to develop resistance to common antibiotics makes managing this type of infections very challenging. Furthermore, oxidative stress is a common consequence of bacterial infection and antibiotic therapy, due to formation of reactive oxygen species (ROS) during their mode of action. In this study we aimed to alleviate oxidative stress and enhance the antibacterial efficacy of ciprofloxacin (CPR) antibiotic by its co -encapsulation with naringin (NAR) within a polyelectrolyte complex (PEX). The PEX comprised of polycationic lactoferrin (LF) and polyanionic pectin (PEC). CPR/NAR-loaded PEX exhibited spherical shape with particle size of 237 ± 3.5 nm, negatively charged zeta potential (−23 ± 2.2 mV) and EE% of 61.2 ± 4.9 for CPR and 76.2 ± 3.4 % for NAR. The LF/PEC complex showed prolonged sequential release profile of CPR to limit bacterial expansion, followed by slow liberation of NAR, which mitigates excess ROS produced by CPR's mechanism of action without affecting its efficacy. Interestingly, this PEX demonstrated good hemocompatibility with no significant in vivo toxicity regarding hepatic and renal functions. In addition, infected mice administrated this nanoplatform intravenously exhibited significant CFU reduction in the lungs and kidneys, along with reduced immunoreactivity against myeloperoxidase. Moreover, this PEX was found to reduce the lungs´ oxidative stress via increasing both glutathione (GSH) and catalase (CAT) levels while lowering malondialdehyde (MDA). In conclusion, CPR/NAR-loaded PEX can offer a promising targeted lung delivery strategy while enhancing the therapeutic outcomes of CPR with reduced oxidative stress. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Thyme essential oil (TEO) was encapsulated in sodium caseinate (Na CAS)/gelatin nanocomposite hydrogel. • Oil-loaded Na CAS/Gelatin nanocomposite hydrogel exhibited sustained release pattern compared to free oil. • Oil-loaded Na CAS micelles exerted enhanced antibacterial activity compared to free TEO and resulted in cell membrane disruption and morphological distortion. • Fabricated nanocomposite hydrogel displayed significant in vivo wound healing potential in terms of reduced inflammation and increased re-epithelialization. Essential oils, derived from aromatic plants, exhibit various pharmacological properties. Nevertheless, their clinical applications are confronted by various limitations, such as chemical instability, low aqueous solubility, and poor bioavailability. Nanoencapsulation is one of the approaches that may circumvent these restraints. Accordingly, the present study encapsulated thyme essential oil (TEO) in sodium caseinate (Na CAS) nanomicelles and formulated a gelatin nanocomposite hydrogel, which was investigated as a drug delivery platform for in vitro antibacterial and in vivo wound healing potential. TEO loaded Na CAS nanomicelles showed particle size of 336 ± 17.35 nm, zeta potential of −44.0 mV and EE% of 75 ± 5%. The release profile of TEO loaded nanocomposite hydrogel revealed a sustained release pattern compared to TEO loaded micelles and free oil. The TEO loaded nanomicelles exhibited a significantly higher antibacterial effect than free TEO, as denoted by leakage of alkaline phosphatase and cell membrane disruptions. Furthermore, the TEO loaded nanocomposite hydrogel significantly promoted wound contraction, reduced interleukin-6, and increased transforming growth factor-β1 and vascular endothelial growth factor levels, versus control or blank hydrogel group. Hence, the present study is putting forth the fabricated nanocomposite hydrogel as a multifunctional delivery system for TEO in wound healing applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sodium casienate micelles were utilized to co-encapsulate vit.D3 and ETP. • The outer surface of the micelles was decorated with an envelope of vit.D3/phosphoatidyl choline phospholipid complex for enhancing their active targeting potential and cellular uptake. • Enhanced in vivo accumulation in tumor tissue in case of vit.D3/ETP micelles. • Superior in vitro and in vivo anticancer activity without any remarkable toxicity. Targeted delivery of cytotoxic drugs has shown great potential in cancer therapy. In this light, vitamin D3 (vit.D3)-coated micelles were fabricated to encapsulate the cytotoxic drug; etoposide (ETP). Sodium caseinate micelles were first utilized to encapsulate vit.D3 and ETP within their hydrophobic core, then drug-loaded micelles were further decorated with an envelope of vit.D3/ phospholipid complex to enhance the active targeting potency of fabricated micelles via exploiting vit.D3 receptors (VDRs) overexpressed on the outer surface of breast cancer cells. In vitro cytotoxicity studies showed that fabricated micelles exhibited improved anticancer effect on MDA MB-231 and MCF-7 human breast cancer cell lines in comparison to free vit.D3 + ETP without any significant toxicity on normal human lung fibroblast (Wi-38) cells. In vivo biodistribution and efficacy studies in Ehrlich ascites tumor animal model revealed that fabricated micelles manifested improved accumulation in tumor tissue due to active targeting potential of vit.D3 without any remarkable toxicity. More importantly, fabricated micelles resulted in enhanced tumor apoptosis, reduced angiogenesis, invasion and autophagy, besides a decline in the tumor expression levels of both miR-21 and miR-192. Therefore, vit.D3/ETP micelles could serve as a favorable actively targeted anticancer delivery system having a superior effect over the free combination. [ABSTRACT FROM AUTHOR]

Much attention has been paid to chitosan biopolymer for advanced wound dressing owing to its exceptional biological characteristics comprising biodegradability, biocompatibility and respectable antibacterial activity. This study intended to develop a new antibacterial membrane based on quaternized aminochitosan (QAMCS) derivative. Herein, aminochitosan (AMCS) derivative was quaternized by N-(2-Chloroethyl) dimethylamine hydrochloride with different ratios. The pre-fabricated membranes were characterized by several analysis tools. The results indicate that maximum surface potential of +42.2 mV was attained by QAMCS3 membrane compared with +33.6 mV for native AMCS membrane. Moreover, membranes displayed higher surface roughness (1.27 ± 0.24 μm) and higher water uptake value (237 ± 8%) for QAMCS3 compared with 0.81 ± 0.08 μm and 165 ± 6% for neat AMCS membranes. Furthermore, the antibacterial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus cereus. Superior antibacterial activities with maximum inhibition values of 80–98% were accomplished by QAMCS3 membranes compared with 57–72% for AMCS membrane. Minimum inhibition concentration (MIC) results denote that the antibacterial activities were significantly boosted with increasing of polymeric sample concentration from 25 to 250 µg/mL. Additionally, all membranes unveiled better biocompatibility and respectable biodegradability, suggesting their possible application for advanced wound dressing. [ABSTRACT FROM AUTHOR]