Antimicrobial Activities of Pistacia lentiscus Essential Oils Nanoencapsulated into Hydroxypropyl-beta-cyclodextrins.

The rising risks of food microbial contamination and foodborne pathogens resistance have prompted an increasing interest in natural antimicrobials as promising alternatives to synthetic antimicrobials. Essential oils (EOs) obtained from natural sources have shown promising anticancer, antimicrobial, and antioxidant activities. EOs extracted from the resins of Pistacia lentiscus var. Chia are widely utilized for the treatment of skin inflammations, gastrointestinal disorders, respiratory infections, wound healing, and cancers. The therapeutic benefits of P. lentiscusessential oils (PO) are limited by their low solubility, poor bioavailability, and high volatility. Nanoencapsulation of PO can improve their physicochemical properties and consequently their therapeutic efficacy while overcoming their undesirable side effects. Hence, PO was extracted from the resins of P. lentiscusvia hydrodistillation. Then, PO was encapsulated into (2-hydroxypropyl)-beta-cyclodextrin (HPßCD) via freeze-drying. The obtained inclusion complexes (PO-ICs) appeared as round vesicles (22.62 to 63.19 nm) forming several agglomerations (180 to 350 nm), as detected by UHR-TEM, with remarkable entrapment efficiency (89.59 ± 1.47%) and a PDI of 0.1475 ± 0.0005. Furthermore, the encapsulation and stability of PO-ICs were confirmed via FE-SEM, 1H NMR, 2D HNMR (NOESY), FT-IR, UHR-TEM, and DSC. DSC revealed a higher thermal stability of the PO-ICs, reaching 351.0 °C. PO-ICs exerted substantial antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as compared to free PO. PO-ICs showed significant enhancement in the antibacterial activity of the encapsulated PO against S. aureus with an MIC90 of 2.84 mg/mL and against P. aeruginosa with MIC90 of 3.62 mg/mL and MIC50 of 0.56 mg/mL. In addition, PO-ICs showed greater antimicrobial activity against E. coli by 6-fold with an MIC90 of 0.89 mg/mL, compared to free PO, which showed an MIC90 of 5.38 mg/mL. In conclusion, the encapsulation of PO into HPßCD enhanced its aqueous solubility, stability, and penetration ability, resulting in a significantly higher antibacterial activity.

Improved antimicrobial activities of Boswellia sacra essential oils nanoencapsulated into hydroxypropyl-beta-cyclodextrins.

Natural antimicrobials have recently gained increasing interest over synthetic antimicrobials to overcome foodborne pathogens and food microbial contamination. Essential oils (EOs) obtained from Boswellia sacra resins (BO) were utilized for respiratory disorders, rheumatoid arthritis, malignant tumors, and viral infections. Like other EOs, the therapeutic potential of BO is hindered by its low solubility and bioavailability, poor stability, and high volatility. Several studies have shown excellent physicochemical properties and outstanding therapeutic capabilities of EOs encapsulated into various nanocarriers. This study extracted BO from B. sacra resins via hydrodistillation and encapsulated it into hydroxypropyl-beta-cyclodextrins (HPßCD) using the freeze-drying method. The developed inclusion complexes of BO (BO-ICs) had high encapsulation efficiency (96.79 ± 1.17%) and a polydispersity index of 0.1045 ± 0.0006. BO-ICs showed presumably spherical vesicles (38.5 to 59.9 nm) forming multiple agglomerations (136.9 to 336.8 nm), as determined by UHR-TEM. Also, the formation and stability of BO-ICs were investigated using DSC, FTIR, FE-SEM, UHR-TEM, 1H NMR, and 2D HNMR (NOESY). BO-ICs showed greater thermal stability (362.7 °C). Moreover, compared to free BO, a remarkable enhancement in the antimicrobial activities of BO-ICs was shown against three different bacteria: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. BO-ICs displayed significant antibacterial activity against Pseudomonas aeruginosa with an MIC90 of 3.93 mg mL-1 and an MIC50 of 0.57 mg mL-1. Also, BO-ICs showed an increase in BO activity against Escherichia coli with an MIC95 of 3.97 mg mL-1, compared to free BO, which failed to show an MIC95. Additionally, BO-ICs showed a more significant activity against Staphylococcus aureus with an MIC95 of 3.92 mg mL-1. BO encapsulation showed significantly improved antimicrobial activities owing to the better stability, bioavailability, and penetration ability imparted by encapsulation into HPßCD.

Recent progress on polySarcosine as an alternative to PEGylation: Synthesis and biomedical applications.

Biotherapeutic PEGylation to prolong action of medications has gained popularity over the last decades. Various hydrophilic natural polymers have been developed to tackle the drawbacks of PEGylation, such as its accelerated blood clearance and non-biodegradability. Polypeptoides, such as polysarcosine (pSar), have been explored as hydrophilic substitutes for PEG. pSar has PEG-like physicochemical characteristics such as water solubility and no reported cytotoxicity and immunogenicity. This review discusses pSar derivatives, synthesis, characterization approaches, biomedical applications, in addition to the challenges and future perspectives of pSar based biomaterials as an alternative to PEG.

Synergistic anticancer effect of Pistacia lentiscus essential oils and 5-Fluorouracil co-loaded onto biodegradable nanofibers against melanoma and breast cancer.

Chemoresistance and severe toxicities represent major drawbacks of chemotherapy. Natural extracts, including the essential oils of Pistacia lentiscus (PLEO), exhibit substantial anticancer and anti-inflammatory activities where different cancers are reported to dramatically recess following targeting with PLEO. PLEO has promising antimicrobial, anticancer, and anti-inflammatory properties. However, the therapeutic properties of PLEO are restricted by limited stability, bioavailability, and targeting ability. PLEO nanoformulation can maximize their physicochemical and therapeutic properties, overcoming their shortcomings. Hence, PLEO was extracted and its chemical composition was determined by GC-MS. PLEO and 5-Fluorouracil (5FU) were electrospun into poly-ε-caprolactone nanofibers (PCL-NFs), of 290.71 nm to 680.95 nm diameter, to investigate their anticancer and potential synergistic activities against triple-negative breast cancer cells (MDA-MB-231), human adenocarcinoma breast cancer cells (MCF-7), and human skin melanoma cell line (A375). The prepared nanofibers (NFs) showed enhanced thermal stability and remarkable physical integrity and tensile strength. Biodegradability studies showed prolonged stability over 42 days, supporting the NFs use as a localized therapy of breast tissues (postmastectomy) or melanoma. Release studies revealed sustainable release behaviors over 168 h, with higher released amounts of 5FU and PLEO at pH 5.4, indicating higher targeting abilities towards cancer tissues. NFs loaded with PLEO showed strong antioxidant properties. Finally, NFs loaded with either PLEO or 5FU depicted greater anticancer activities compared to free compounds. The highest anticancer activities were observed with NFs co-loaded with PLEO and 5FU. The developed 5FU-PLEO-PCL-NFs hold potential as a local treatment of breast cancer tissues (post-mastectomy) and melanoma to minimize their  possible recurrence.

PEGylated Chitosan Nanoparticles Loaded with Betaine and Nedaplatin Hamper Breast Cancer: In Vitro and In Vivo Studies.

The current study investigates the anticancer effects of PEGylated chitosan nanoparticles (CS NPs) coloaded with betaine (BT) and nedaplatin (ND) on breast adenocarcinoma (MCF-7) cells and breast cancer-bearing rats. Hereof, the ionotropic gelation approach was implemented for the synthesis of PEG-uncoated and PEG-coated CS NPs encompassing either BT, ND, or both (BT-ND). The sizes of the developed BT/CS NPs, ND/CS NPs, and BT-ND/CS NPs were 176.84 ± 7.45, 204.1 ± 13.6, and 201.1 ± 23.35 nm, respectively. Meanwhile, the sizes of the synthesized BT/PEG-CS NPs, ND/PEG-CS NPs, and BT-ND/PEG-CS NPs were 165.1 ± 32.40, 148.2 ± 20.98, and 143.7 ± 7.72 nm, respectively. The surface charges of the fabricated nanoparticles were considerably high. All of the synthesized nanoparticles displayed a spherical form and significant entrapment efficiency. Release experiments demonstrated that the PEGylated and non-PEGylated CS NPs could discharge their contents into the tumor cells' microenvironments (pH 5.5). In addition, the NPs demonstrated an outstanding ability to reduce the viability of the MCF-7 cell line. In addition, BT-ND/PEG-CS NPs were found to be the strongest among all NP preparations, where they caused around 90% decrease in the size of mammary gland tumors in rats compared to vehicle-treated animals.

Cytotoxic and Antioxidative Effects of Geranium Oil and Ascorbic Acid Coloaded in Niosomes against MCF-7 Breast Cancer Cells.

Geranium oil (GO) has antiproliferative, antiangiogenic, and anti-inflammatory properties. Ascorbic acid (AA) is reported to inhibit the formation of reactive oxygen species, sensitize cancer cells, and induce apoptosis. In this context, AA, GO, and AA-GO were loaded into niosomal nanovesicles to ameliorate the physicochemical properties of GO and improve its cytotoxic effects using the thin-film hydration technique. The prepared nanovesicles had a spherical shape with average diameters ranging from 200 to 300 nm and exhibited outstanding surface negative charges, high entrapment efficiencies, and a controlled sustained release over 72 h. Entrapping AA and GO in niosomes resulted in a lower IC50 value than free AA and GO when tested on MCF-7 breast cancer cells. In addition, flow cytometry analysis showed higher apoptotic cells in the late apoptotic stage upon treating the MCF-7 breast cancer cells with AA-GO niosomal vesicles compared to treatments with free AA, free GO, and AA or GO loaded into niosomal nanovesicles. Assessing the antioxidant effect of the free drugs and loaded niosomal nanovesicles showed enhanced antioxidant activity of AA-GO niosomal vesicles. These findings suggest the AA-GO niosomal vesicles as a potential treatment strategy against breast cancer, possibly through scavenging free radicals.

A novel long-acting antimicrobial nanomicelle spray.

Contaminated surfaces play a major role in disease transmission to humans. The vast majority of commercial disinfectants provide short-term protection of surfaces against microbial contamination. The Covid-19 pandemic has attracted attention to the importance of long-term disinfectants as they would reduce the need for staff and save time. In this study, nanoemulsions and nanomicelles containing a combination of benzalkonium chloride (BKC; a potent disinfectant and a surfactant) and benzoyl peroxide (BPO; a stable form of peroxide that is activated upon contact with lipid/membranous material) were formulated. The prepared nanoemulsion and nanomicelle formulas were of small sizes <80 nm and high positive charge >45 mV. They showed enhanced stability and prolonged antimicrobial efficacy. The antibacterial potency was evaluated in terms of long-term disinfection on surfaces as verified by repeated bacterial inoculums. Additionally, the efficacy of killing bacteria upon contact was also investigated. A nanomicelle formula (NM-3) consisting of 0.8% BPO in acetone and 2% BKC plus 1% TX-100 in distilled water (1 : 5 volume ratio) demonstrated overall surface protection over a period of 7 weeks upon a single spray application. Furthermore, its antiviral activity was tested by the embryo chick development assay. The prepared NM-3 nanoformula spray showed strong antibacterial activities against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus as well as antiviral activities against infectious bronchitis virus due to the dual effects of BKC and BPO. The prepared NM-3 spray shows great potential as an effective solution for prolonged surface protection against multiple pathogens.

Effect of mold shape on the microstructure of gelatin sponges for tissue engineering applications.

Gelatin sponges have been used in several medical applications including tissue replacement, scaffolds, and hemostasis. Each application requires specific parameters that are tuned by the porosity of the sponges. Therefore, changes in the porosity profile of the sponges would change the sponge behavior. In this study, a gelatin solution was prepared and crosslinked with glutaraldehyde. Afterward, the solution was poured into three different mold structures with different volumes and frozen at a constant freezing rate. Each mold was investigated for its physical characteristics including swelling, degradation, porosity, crystallinity, and mechanical compression. Cube-molded gelatin sponges demonstrated high swelling capacity, degradation rate, and porosity while exhibiting low crystallinity, yield strength, and elasticity. These characteristics are suitable for hemostatic application and tissue regeneration. Therefore, it is recommended to freeze dry gelatin sponge in cuboid-shaped dimensions, for research or industry, to control the porosity and crystallinity of the sponge for the best result in biomedical applications.

Enzyme Immobilization Technologies and Industrial Applications.

Enzymes play vital roles in diverse industrial sectors and are essential components of many industrial products. Immobilized enzymes possess higher resistance to environmental changes and can be recovered/recycled easily when compared to the free forms. The primary benefit of immobilization is protecting the enzymes from the harsh environmental conditions (e.g., elevated temperatures, extreme pH values, etc.). The immobilized enzymes can be utilized in various large-scale industries, e.g., medical, food, detergent, textile, and pharmaceutical industries, besides being used in water treatment plants. According to the required application, a suitable enzyme immobilization technique and suitable carrier materials are chosen. Enzyme immobilization techniques involve covalent binding, encapsulation, entrapment, adsorption, etc. This review mainly covers enzyme immobilization by various techniques and their usage in different industrial applications starting from 1992 until 2022. It also focuses on the multiscale operation of immobilized enzymes to maximize yields of certain products. Lastly, the severe consequence of the COVID-19 pandemic on global enzyme production is briefly discussed.

Multi-responsive paper chemosensors based on mesoporous silica nanospheres for quantitative sensing of heavy metals in water.

Exposure to low concentrations of heavy metal cations seriously harms living organisms, hence they are considered environmental toxins. Portable simple detection systems are required for field monitoring of multiple metal ions. In this report, paper-based chemosensors (PBCs) were prepared by adsorbing 1-(pyridin-2-yl diazenyl) naphthalen-2-ol (chromophore), which recognizes heavy metals, onto filter papers coated with mesoporous silica nano spheres (MSNs). The high density of the chromophore probe on the surface of PBCs resulted in ultra-sensitive optical detection of heavy metal ions and short response time. The concentration of metal ions was determined using digital image-based colorimetric analysis (DICA) and compared to spectrophotometry under optimal sensing conditions. The PBCs exhibited stability and short recovery times. The detection limits determined using DICA of Cd2+, Co2+, Ni2+ and Fe3+ were 0.22, 0.28, 0.44, and 0.54 µM; respectively. Additionally, the linear ranges for monitoring Cd2+, Co2+, Ni2+ and Fe3+ were 0.44-4.4, 0.16-4.2, 0.8-8.5, and 0.002-5.2 µM; respectively. The developed chemosensors showed high stability, selectivity, and sensitivity for sensing of Cd2+, Co2+, Ni2+ and Fe3+ in water under optimum conditions and hold potential for low cost, onsite sensing of toxic metals in water.

Essential Oils Extracted from Boswellia sacra Oleo Gum Resin Loaded into PLGA-PCL Nanoparticles: Enhanced Cytotoxic and Apoptotic Effects against Breast Cancer Cells.

This work aims to develop and optimize blended polylactide-co-glycolide (PLGA) and poly(ε-caprolactone, PCL) loaded with Boswellia sacra oil (BO) to improve BO's physicochemical properties and anti-breast cancer effects via enhancing apoptosis. In this context, BO was extracted from B. sacra oleo gum resins (BO) via hydrodistillation and chemically characterized by evaluating its essential oil's composition using gas chromatography-mass spectrometry. Then, BO/PLGA-PCL NPs were formulated using the emulsion (O/W) solvent evaporation technique using a PLGA-PCL mixture at five different ratios (1:1, 2:1, 3:1, 1:2, and 1:3, respectively). The optimized NPs had a spherical morphology with no agglomerations and the lowest hydrodynamic size (230.3 ± 3.7 nm) and polydispersity index (0.13 ± 0.03) and the highest ζ potential (-20.36 ± 4.89 mV), as compared to the rest of the formulas. PLGA-PCL NPs could entrap 80.59 ± 3.37% of the BO and exhibited a controlled, sustained release of BO (83.74 ± 3.34%) over 72 h. Encapsulating BO in the form of BO/PLGA-PCL NPs resulted in a lower IC50 value as assessed by the MTT assay. Furthermore and upon assessing the apoptotic effect of both BO and BO/PLGA-PCL NPs, there was an increase in the percentage of apoptotic and necrotic cell percentages compared to the control and free BO. Encapsulation of BO in PLGA-PCL NPs doubled the percentage of apoptotic and necrotic cells exerted by free BO. These findings support the potential use of BO/PLGA-PCL NPs in treating breast cancer.

Polymeric nanoparticles for dopamine and levodopa replacement in Parkinson's disease.

As the world's population ages, the incidence of Parkinson's disease (PD), the second most common neurological ailment, keeps increasing. It is estimated that 1% of the global population over the age of 60 has the disease. The continuous loss of dopaminergic neurons and the concomitant brain depletion of dopamine levels represent the hallmarks of PD. As a result, current PD therapies primarily target dopamine or its precursor (levodopa). Therapeutic approaches that aim to provide an exogenous source of levodopa or dopamine are hindered by their poor bioavailability and the blood-brain barrier. Nevertheless, the fabrication of many polymeric nanoparticles has been exploited to deliver several drugs inside the brain. In addition to a brief introduction of PD and its current therapeutic approaches, this review covers novel polymeric nanoparticulate drug delivery systems exploited lately for dopamine and levodopa replacement in PD.

Ozonated Olive Oil: Enhanced Cutaneous Delivery via Niosomal Nanovesicles for Melanoma Treatment.

Ozonated olive oil (OL) combines the therapeutic effects of both ozone and olive oil. However, it suffers from limited water solubility and poor transdermal permeation, which hinder its application in melanoma treatment. Nanocarrier host molecules, such as niosomes, were used to improve the water solubility, transdermal permeation, and anticancer effect of hydrophobic compounds. This study aims to design and optimize a niosomal vesicular nanoplatform loaded with OL (OL/NSs) to improve OL's skin permeation and anti-melanoma effect. In this regard, OL was prepared and characterized by evaluating its chemical properties (acid, peroxide, and iodine values) and fatty acid composition using gas chromatography. Then, OL/NSs were developed using the thin film hydration method employing cholesterol, Span 60, and Tween 60 at five different molar ratios. The optimized niosomes had an average diameter of 125.34 ± 13.29 nm, a surface charge of -11.34 ± 4.71 mV, and a spherical shape. They could entrap 87.30 ± 4.95% of the OL. OL/NSs showed a 75% sustained oil release over 24 h. The skin permeation percentage of OL/NSs was 36.78 ± 3.31 and 53.44 ± 6.41% at 12 and 24 h, respectively, three times higher than that of the free OL (11.50 ± 1.3 and 17.24 ± 2.06%, at 12 and 24 h, respectively). Additionally, the anticancer activity of the developed niosmal formulation, when tested on human melanoma cells (A375), was double that of the free OL; the IC50 of the OL/NSs was 8.63 ± 2.8 µg/mL, and that of the free OL was 17.4 ± 3.7 µg/mL. In conclusion, the encapsulation of ozonated olive oil in niosomes enhanced its water solubility, skin permeation, and anticancer activity and thus may represent potent natural chemotherapy in treating melanoma.

Monitoring of Cobalt and Cadmium in Daily Cosmetics Using Powder and Paper Optical Chemosensors.

Daily used cosmetics may contain high levels of heavy metals which are added to improve the quality and shine of cosmetics but represent a threat to human health. In this report, powder- and paper-based optical nanosensors using mesoporous silica nanospheres as carriers were designed for determination of Co2+ and Cd2+ in commonly used cosmetics. Powder optical chemosensors (POCs) were prepared via direct decoration of optical probes into a porous carrier. Paper-based chemosensors (PBCs) were designed via adsorbing the organic chromophore onto filter papers treated with mesoporous silica. POCs and PBCs were constructed with thick decoration of optical probes, leading to the formation of active surface centers for monitoring of Co2+ and Cd2+ in cosmetic products. The uniform structures of POCs and PBCs have resulted in selective sensing and low detection limits up to parts per billion, wide detection range determination, and fast response (on the order of seconds). Digital image colorimetric analysis (DICA) was used to quantify the color of PBCs and deduce the corresponding concentrations of Co2+ and Cd2+ using calibration curves. DICA data correlated well with that obtained from UV-vis spectrophotometry. The developed POCs and PBCs showed wide detection ranges of metal ions and a considerably low detection limit under optimal analysis conditions. The low limit of detection of Co2+ and Cd2+ ions using POCs was 6.7 × 10-9 and 3.5 × 10-9 M, respectively. To the best of our knowledge, this is the first time simple PBCs have been designed for monitoring Co2+ and Cd2+ with detection limits of 2.2 × 10-7 and 1.3 × 10-7 M. A limited amount of manufactured POCs (about 20 mg) were used for all measurements, and commercial filter paper treated with mesoporous nanosphere silica was used for sensing Co2+ and Cd2+ ions. The developed optical chemosensors had short regeneration times and exhibited high stability and surface functionality and are capable of monitoring Co2+ and Cd2+ in various cosmetic products.

Fast detection of bacterial contamination in fresh produce using FTIR and spectral classification.

Screening for microbial contaminants in fresh produce is a lengthy process relative to their short shelf-life. The aim of this study is to develop a comprehensive assay which employs FTIR and spectral classification algorithm for detection of bacterial contamination of fresh produce. The procedure starts by soaking a sample of the fresh produce in broth for 5 h. Then, magnetic nanoparticles are added to capture bacteria which are then collected and prepared for FTIR scanning. The generated FTIR spectra are compared against an in-house database of different bacterial species (n = 6). The ability of the database to discriminate contaminated and uncontaminated samples and to identify the bacterial species was assessed. The compatibility of the FTIR procedures with subsequent DNA extraction and PCR was tested. The developed procedure was applied for assessment of bacterial contamination in fresh produce samples from the market (n = 78). Results were compared to the conventional culture methods. The generated FTIR database coupled to spectral classification was able to detect bacterial contamination with overall accuracy exceeding 90%. The sample processing did not alter the integrity of the bacterial DNA which was suitable for PCR. On application to fresh produce samples collected from the market, the developed method was able to detect bacterial contamination with 94% concordance with the culture method. In conclusion, the developed procedure can be applied for fast detection of microbial contamination in fresh produce with comparable accuracy to conventional microbiological assays and is compatible with subsequent molecular assays.

PEGylated Chitosan Nanoparticles Encapsulating Ascorbic Acid and Oxaliplatin Exhibit Dramatic Apoptotic Effects against Breast Cancer Cells.

This study aims to design a pH-responsive dual-loaded nanosystem based on PEGylated chitosan nanoparticles loaded with ascorbic acid (AA) and oxaliplatin (OX) for the effective treatment of breast cancer. In this regard, non-PEGylated and PEGylated chitosan nanoparticles (CS NPs) loaded with either ascorbic acid (AA), oxaliplatin (OX), or dual-loaded with AA-OX were fabricated using the ionotropic gelation method. The hydrodynamic diameters of the fabricated AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs were 157.20 ± 2.40, 188.10 ± 9.70, and 261.10 ± 9.19 nm, respectively. While the hydrodynamic diameters of the designed AA/PEG-CS NPs, OX/PEG-CS NPs, and AA-OX/PEG-CS NPs were 152.20 ± 2.40, 156.60 ± 4.82, and 176.00 ± 4.21 nm, respectively. The ζ-potential of the prepared nanoparticles demonstrated high positive surface charges of +22.02 ± 1.50, +22.58 ± 1.85 and +40.4 ± 2.71 mV for AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs, respectively. The ζ-potential of the PEGylated CS NPs was reduced owing to the shielding of the positive charges by the PEG chains. Additionally, all the prepared nanoparticles exhibited high entrapment efficiencies (EE%) and spherical-shaped morphology. The chemical features of the prepared nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy. Release studies showed the capability of the prepared non-PEGylated and PEGylated chitosan NPs to release their cargo in the acidic environment of cancer tissue (pH 5.5). Furthermore, the AA/CS NPs, AA/PEG-CS NPs, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs and AA-OX/PEG-CS NPs exhibited remarkable cytotoxic activities against breast adenocarcinoma (MCF-7) cells with IC50 values of 44.87 ± 11.49, 23.3 ± 3.73, 23.88 ± 6.29, 17.98 ± 3.99, 18.69 ± 2.22, and 7.5 ± 0.69 µg/mL, respectively; as compared to free AA and OX (IC50 of 150.80 ± 26.50 and 147.70 ± 63.91 µg/mL, respectively). Additionally, treatment of MCF-7 cells with IC50 concentrations of AA, AA/CS NPs, AA/PEG-CS NPs, OX, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs or AA-OX/PEG-CS NPs increased the percentages of early apoptotic cells to 5.28%, 9.53%, 11.20%, 5.27%, 13.80%, 8.43%, 2.32%, and 10.10%, respectively, and increased the percentages of late apoptotic cells to 0.98%, 0.37%, 2.41%, 2.06%, 0.97%, 9.66%, 56%, and 81.50%, respectively. These results clearly indicate that PEGylation enhances the apoptotic effect of AA and OX alone, in addition to potentiating the apoptotic effect of AA and OX when combined on MCF-7 cells. In conclusion, PEGylated chitosan nanoparticles encapsulating AA, OX, or AA and OX represent an effective formula for induction of apoptosis in MCF-7 cells.

Enhanced Anticancer Activity of Nedaplatin Loaded onto Copper Nanoparticles Synthesized Using Red Algae.

Marine algae are a rich source of biologically active compounds that can be utilized in various food and pharmaceutical applications. In this study, ultrasound-assisted extraction (UAE) was optimized to maximize yield and total carbohydrate content extracted from the red algae, Pterocladia capillacea. The extract was shown to possess potent antioxidant activity of up to ~70%, and was successfully used as a reducing and capping agent in the green synthesis of copper nanoparticles, which were characterized by UV-spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Primarily, CuO nanoparticles with an average size of 62 nm were produced. FTIR spectra for the extract and algal-mediated CuO nanoparticles showed characteristic polysaccharide peaks. The synthesized CuO nanoparticles were subsequently loaded with nedaplatin where UV data suggested a complex formation. Nedaplatin release profiles showed a sustained release that reached a maximum at 120 h. The formulation was shown to have greater cytotoxicity relative to nedaplatin on hepatocellular carcinoma, breast cancer and ovarian cancer cell lines with IC50 values of 0.40 ± 0.08, 1.50 ± 0.12, and 0.70 ± 0.09 µg/mL, respectively. Loading nedaplatin onto CuO nanoparticles synthesized using red algae extract, greatly enhances its anticancer effect.

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin.

Para-sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin. Furthermore, it has been characterized using 1H NMR, mass spectrometry, elemental analysis, and UHPLC. A host-guest complex of asplatin and p-sulfocalix[4]arene (PSC4) has been developed and characterized using UV, Job's plot analysis, HPLC, and density functional theory (DFT) calculations. The experimental and computational investigations propose that a 1:1 complex between asplatin and PSC4 is formed. The stability constant of the designed complex has been determined using Job's plot and UHPLC and computed to be 9.1 × 104 M-1 and 8.7 × 104 M-1, which corresponds to a free energy of complexation of -6.8 kcal mol-1, while the calculated value for the inclusion free energy is -13.2 kcal mol-1. Both experimentally and theoretically estimated complexation free energy show that a stable host-guest complex can be formed in solution. The in vitro drug release study displayed the ability of the complex to release its cargo at a cancerous pH (pH of 5.5). Additionally, the asplatin/PSC4 complex is shown to be biocompatible when tested on human skin fibroblast noncancerous cells, demonstrating the highest in vitro cytotoxic activity against (MCF-7), cervical (HeLa), and lung cancer cells (A-549), with IC50 values of 0.75, 2.15, and 3.60 µg/mL, respectively. This is as compared to either cisplatin (IC50 of 5.47, 5.94 and 9.61 µg/mL, respectively) or asplatin (IC50 of 1.54, 5.05 and 3.91 µg/mL, respectively). On the other hand, the free asplatin exhibited higher cytotoxicity on cancerous cells and lower toxicity on noncancerous cells. The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent.

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities.

Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-ß-cyclodextrin (HPßCD)/harmala alkaloid-rich fraction (HARF) host-guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF-HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF-HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 µg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD-HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT.