Enhanced anti-tumor and anti-metastatic activity of quercetin using pH-sensitive Alginate@ZIF-8 nanocomposites:in vitroandin vivostudy.

Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of Qc. The developed alginate-modified quercetin-loaded ZIF-8 (Alg@Qc@ZIF-8) was characterized using scanning electron microscope (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy Thermogravimetric analysis, Brunauer-Emmett-Teller, and x-ray diffraction. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, -23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02%. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more Qc at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 h. Furthermore, the IC50value of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net Qc. Considering thein vitroandin vivooutcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management.

Targeted drug delivery via folate decorated nanocarriers based on linear polymer for treatment of breast cancer.

In this project, a biocompatible block copolymer including poly ethylene glycol and poly caprolactone was synthesized using ring-opening reaction. Then, the copolymer was conjugated to folic acid using lysine as a linker. Also, curcumin (CUR) was used as a therapeutic anticancer agent. Nanoprecipitation method was used to prepare CUR-loaded polymeric micelles. Different methods including Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the prepared nanocarriers (NCs). MTT assay and hemolysis assay were used to evaluate in vitro anticancer efficiency and biocompatibility of the prepared NCs, respectively. The results proved efficiency of NCs as a drug delivery system (DDS) in various aspects such as physicochemical properties and biocompatibility. Also, in vivo results showed that NCs did not show any severe weight loss and side effects on mice, and the anti-cancer study results of the CUR-loaded NCs proved that the conjugation of folic acid on the surface of NCs as a targeting agent could increase the therapeutic efficacy of CUR.

In vitro evaluation of albendazole-loaded nanostructured lipid carriers on Echinococcus granulosus microcysts and their prophylactic efficacy on experimental secondary hydatidosis.

To enhance the therapeutic effects of albendazole (ABZ) on Echinococcus granulosus protoscoleces and metacestodes, ABZ-loaded nanostructured lipid carriers (ABZ-NLCs) are prepared by the hot high-speed homogenization method. Protoscoleces and microcysts were treated in vitro with free ABZ and ABZ-NLCs (concentrations of 1, 5, and 10 µg/ml), and the corresponding effects were monitored by methylene blue exclusion test and scanning and transmission electron microscopy. Chemoprophylactic treatment was performed on Balb/C mice 1 day before intraperitoneal injection of viable protoscoleces. The drugs were administered daily by intragastric inoculation for a period of 30 days. The prophylactic efficacy was assessed based on the number and weight of cysts developed in treated mice. The ultrastructural alterations in cysts were examined by transmission electron microscopy. After 18 days, all the protoscoleces incubated with 10 µg/ml ABZ-NLCs were killed, while 51.25 ± 4.03% of the protoscoleces incubated with 10 µg/ml free ABZ were still viable. Microcysts treated with ABZ-NLCs underwent degenerative alterations in a shorter time than when free ABZ was applied. The mean weight of the cysts recovered from mice of ABZ-NLCs group was significantly lower than that of the free ABZ group (P < 0.05), yielding prophylactic efficacy of 92.45% and 38.53%, respectively. The cysts treated with ABZ-NLCs showed marked ultrastructural changes in the germinal layer. This study demonstrated that both in vitro and in vivo treatments with ABZ-NLCs are significantly more efficient than treatment with free ABZ against E. granulosus protoscoleces, metacestodes, and prevention of cyst development in mice.

Effect of corn starch coating incorporated with nanoemulsion of Zataria multiflora essential oil fortified with cinnamaldehyde on microbial quality of fresh chicken meat and fate of inoculated Listeria monocytogenes.

The present study compared the effects of corn starch coatings incorporated with Zataria multiflora essential oil (ZEO) and cinnamaldehyde (CIN) in conventional, nanoemulsion (NZEO) and fortified nanoemulsion (NZEOC) forms, on specific spoilage microorganisms of chicken meat and on the fate of inoculated Listeria monocytogenes during 20 days storage at 4 ± 1 °C. Based on the results of GC-MS analysis of ZEO, carvacrol (36.62%) was the most important compound of essential oil. Samples coated with the starch solution containing nanoemulsions had better antimicrobial activities than conventional forms. Also, NZEOC treatment had the best antimicrobial properties at the end of storage with the following results: Total viable count (7.96 log10 CFU/g), Psychrotrophic count (7.29 log10 CFU/g), Lactic acid bacteria (6.51 log10 CFU/g), Enterobacteriaceae count (6.98 log10 CFU/g), Mold and yeast count (5.16 log10 CFU/g) and inoculated L. monocytogenes (6.51 log10 CFU/g). Furthermore, the addition of CIN-ZEO during nanoemulsion formation (NZEOC) increased the antimicrobial properties of the samples compared to individual addition of NZEO and CIN (NZEO + CIN) to the starch solution. Therefore, corn starch coating containing NZEOC is recommended as a natural preservative to enhance the microbial stability of poultry meat.

The Comparison of Antimicrobial Effect of Nigella sativa Nanoparticle and Chlorhexidine Emulsion on the Most Common Dental Cariogenicic Bacteria.

Background: Tooth decay and periodontal disease are the most common chronic human and oral diseases, respectively, and bacterial plaque has a major role in their occurrence. Because of the importance of plaque control, this study was done to compare the antimicrobial effects of Nigella sativa nanoparticles and chlorhexidine emulsion on the most common dental cariogenicic bacteria. Methods: In this experimental study, the effects of 0.2% chlorhexidine mouthwash and Nigella sativa nanoparticle with different dilutions on Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Lactobacillus acidophilus, Minococcal fecalis, and Enterococcus fecalis were compared using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assessment. Data were analyzed by SPSS Version 16.0 software, and statistical tests, including an independent sample t test. Results: Mean diameters of growth inhibition zone because of the nanoemulsion of Nigella sativa nanoparticle was close to each other in different bacteria (p=0.665). In addition, there was no significant difference between these values because of different dilutions of nanoemulsion even in different microbial species (p=0.778). The MIC and lethal concentrations of Nigella sativa nanoemulsion were similar for Enterococcus faecalis and Streptococcus mutans, and it was higher than other bacteria. In comparison, the MIC and MBC values of all bacteria in chlorhexidine were lower than those of the nanoemulsion. Conclusion: MIC and MBC values showed that Nigella sativa nanoemulsion affects tooth cariogenicic bacteria. Enterococcus faecalis and Lactobacillus acidophilus were the most resistant and susceptible bacteria to this nanoparticle, respectively, while the antimicrobial effects of Nigella sativa nanoemulsion were weaker than the chlorhexidine mouthwash.

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement.

OBJECTIVE: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood-brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain. METHODS: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method. RESULTS: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112 ± 3.5 nm, 0.20 ± 0.02, and -33.2 ± 2.6 mV, respectively. From in vivo studies in animal model of rats, the AUC0-4 h of brain concentration-time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug. CONCLUSIONS: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.

Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs' Dosage Ratio Effect.

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

Synthesis, characterization, and kinetic release study of methotrexate loaded mPEG-PCL polymersomes for inhibition of MCF-7 breast cancer cell line.

In this study, we designed a polymersome system for the controlled release of methotrexate (MTX) as an anticancer drug with the objective of improving the loading efficiency of the drug in polymersomes as well as achievement of an efficient control on the release rate of drug from nanocarriers. We synthesized mono methoxy poly(ethylene glycol)-poly(e-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) techniques. MTX was encapsulated within nanoparticles (NPs) through multiple emulsion method. The resulting NPs were characterized further by various techniques such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Next, the various kinetic equations were fitted to the release data of MTX from MTX-loaded mPEG-PCL polymersomes. The results showed that the zeta potential of MTX-loaded mPEG-PCL polymersomes was about -5.49 mV and the average size was 49.18 nm. MTX was encapsulated into polymersomes loading capacity of 12 ± 0.09% and encapsulation efficiency of 45.5 ± 0.41%. The metabolic activity assays of void of MTX, mPEG-PCL polymersomes, and MTX-loaded mPEG-PCL polymersomes were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell lines. It can be concluded that application of NPs is a better and more effective strategy for controlled and slow release of MTX in the treatment of cancer.

Curcumin mediated down-regulation of αV ß3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells.

Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of αv ß3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib. Curcumin-loaded Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib-loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step nanoprecipitation method and used as combination therapy of resistant SW480 cancer cells. After that, gene expression levels of PDK4, αv, and ß3 mRNA were determined by the semiquantitative reverse transcription-polymerase chain reaction. Protein levels of whole αv ß3 integrin were evaluated using the enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of nonresistant and resistant cells was 87.6 ± 1.2 nM and 19.1 ± 0.14 µM, for erlotinib and it was about 21.8 and 30 µM for curcumin, respectively. Although PDK4 expression was not significantly different in resistant and nonresistant cells, its expression was up regulated (1.4 fold) in resistant cells by a combination therapy of cur/mPEG-PCL at a dose of 3 µM and erl/mPEG-PCL at a dose of 5 µM. ß3 mRNA and the protein level of whole αv ß3 integrin was significantly higher in resistant SW480 cells as compared with those in nonresistant cells. In terms of treatment, a combination of 6-µM cur/mPEG-PCL and 5-µM erl/mPEG-PCL down regulated ß3 gene expression 6.6-fold in resistant cells as compared with nonresistant cells. At the protein level, a combination of 3-µM-cur/mPEG-PCL and 10-µM erl/mPEG-PCL reduced αv ß3 protein in resistant cells. The results indicated that combination therapy using cur/mPEG-PCL and erl/mPEG-PCL could decrease αv ß3 integrin expression and increase PDK4 gene expression in resistant colon cancer cells, which may have effects on drug resistance signaling pathways.

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG-PCLNanoparticles.

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG-PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG-PCL(DOX-mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX-mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG-PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.

Novel pH-responsive alginate-stabilized curcumin-selenium-ZIF-8 nanocomposites for synergistic breast cancer therapy.

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy.

Biomaterials coated with zwitterionic polymer brush demonstrated significant resistance to bacterial adhesion and biofilm formation in comparison to brush coatings incorporated with antibiotics.

A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.

Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

Bovine serum albumin-coated ZIF-8 nanoparticles to enhance antitumor and antimetastatic activity of methotrexate: in vitro and in vivo study.

In this study, a bovine serum albumin-decorated zeolitic imidazolate framework (ZIF-8@BSA) was used to enhance the anticancer and antimetastatic properties of methotrexate. SEM, DLS, FT-IR, and XRD confirmed the physicochemical suitability of the developed nanoparticles. According to the SEM analysis, the mean size of ZIF-8 nanoparticles was 68.5 ± 13.31 nm. The loading capacity and encapsulation efficiency of MTX@ZIF-8@BSA were 28.77 ± 2.54% and 96.3 ± 0.67%, respectively. According to the in vitro hemolysis test, MTX@ZIF-8@BSA showed excellent blood compatibility. MTX@ZIF-8@BSA exhibited pH sensitivity, releasing more MTX at pH 5.4 (1.73 times) than at pH 7.4. The IC50 value of MTX@ZIF-8@BSA on 4T1 cells was 32.7 ± 7.3 µg/mL after 48 h of treatment, outperforming compared to free MTX with an IC50 value of 53.3 ± 3.7 µg/mL. Treatment with MTX@ZIF-8@BSA resulted in superior tumor growth suppression in tumor-bearing mice than free MTX. Furthermore, based on histopathology tests, MTX@ZIF-8@BSA reduced the metastasis in lung and liver tissues. While there was not any noticeable toxicity in the vital organs of MTX@ZIF-8@BSA-receiving mice, free methotrexate resulted in severe toxicity in the kidneys and liver. According to the preliminary in vitro and in vivo findings, MTX@ZIF-8@BSA presents an attractive drug delivery system candidate for breast cancer due to its enhanced antitumor efficacy and lower toxicity.

Poly-ε-caprolactone (PCL)/poly-l-lactic acid (PLLA) nanofibers loaded by nanoparticles-containing TGF-ß1 with linearly arranged transforming structure as a scaffold in cartilage tissue engineering.

This study aimed to present a novel three-dimensional nanocomposite scaffold using poly-ε-caprolactone (PCL), containing transforming growth factor-beta 1 (TGF-ß1)-loaded chitosan-dextran nanoparticles and poly-l-lactic acid (PLLA), to make use of nanofibers and nanoparticles simultaneously. The electrospinning method fabricated a bead-free semi-aligned nanofiber composed of PLLA, PCL, and chitosan-dextran nanoparticles containing TGF-ß1. A biomimetic scaffold was constructed with the desired mechanical properties, high hydrophilicity, and high porosity. Transmission electron microscopy findings showed a linear arrangement of nanoparticles along the core of fibers. Based on the results, burst release was not observed. The maximum release was achieved within 4 days, and sustained release was up to 21 days. The qRT-PCR results indicated an increase in the expression of aggrecan and collagen type Ι genes compared to the tissue culture polystyrene group. The results indicated the importance of topography and the sustained release of TGF-ß1 from bifunctional scaffolds in directing the stem cell fate in cartilage tissue engineering.

Immunogenic Evaluation of MPEG-PCL & PLGA Nanoparticles Containing Klebsiella pneumoniae K2O1 Capsular Antigen in Pulmonary Infection Model of Mice.

Klebsiella pneumoniae can cause destructive changes to human lungs if aspirated. The present study aimed to evaluate the immunogenicity of the carriers of Poly lactic-co-glycolic acid (PLGA) and Methoxypoly(ethylene glycol) Poly(caprolactone) (MPEG-PCL) nanoparticles containing the capsular antigen of Klebsiella pneumoniae K2O1 in a model of pulmonary infection in mice as a vaccine candidate. Capsule antigen was extracted from K.pneumoniae K2O1 strain 1053 ATCC 10031 and transported with PLGA or MPEG-PCL nanoparticles as a vaccine in an animal model. The results of FT-IR and AFM confirmed the presence of antigen functional groups in the nanoparticle structure, and semi-spherical shape of the nanoparticles, respectively. The capsular polysaccharide was also used to evaluate the febrileness of the designed vaccine candidates based on the rabbits' pattern, and mortality due to the vaccine candidates in the mice. No fever was observed, and no mortality was observed in the mice. According to the results, the vaccine candidates designed to control the cause of pulmonary infections were effective in the liver, spleen, and lungs of the animals with the ability to enter the first stage of the clinical trial phase.

Valine conjugated polymeric nanocarriers for targeted co-delivery of rivastigmine and quercetin in rat model of Alzheimer disease.

Multifunctional nanocarriers are increasingly promising for disease treatment aimed at finding effective therapy and overcoming barriers in drug delivery. Herein, valine conjugated chitosan (VLCS) was used for surface modification of nanocarriers (NCs) based on Poly (ε-caprolactone)-Poly (ethylene glycol)-Poly (ε-caprolactone) (PCL-PEG-PCL) triblock copolymers (NCs@VLCS). The nanocarriers were co-loaded with rivastigmine (RV) and quercetin (QT) to yield the final RV/QT-NCs@VLCS as a multifunctional nanocarrier for Alzheimer's disease (AD) treatment. The large amino acid transporter 1 (LAT-1) was selected for the direction of the NCs to the brain. The biocompatibility of the nanocarrier was studied in HEK-293 and SH-SY5Y cells and rats. The Morris water maze test demonstrated a faster regain of memory loss with RV/QT-NCs@VLCS compared to the other groups. Furthermore, RV/QT-NCs@VLCS and RV/QT-NCs improved GSH depletion induced by scopolamine (SCO), with RV/QT-NCs@VLCS having a superior effect. The real-time PCR analysis revealed that co-delivery of RV and QT by NCs@VLCS showed significantly higher efficacy than sole delivery of RV. RV/QT-NCs@VLCS treatment also modulated the expression of BDNF, ACHE, and TNF-α. The findings revealed that NCs@VLCS co-loaded with RV and QT, significantly increased efficacy relative to the single use of RV and could be considered a potent multifunctional drug delivery system for Alzheimer's treatment.

Chitosan-decorated and tripolyphosphate-crosslinked pH-sensitive niosomal nanogels for Controlled release of fluoropyrimidine 5-fluorouracil.

In the present study, 5-fluorouracil-loaded niosomal nanoparticles were successfully prepared and coated with chitosan and subsequently crosslinked by tripolyphosphate to form niosomal nanogels. The prepared niosomal formulations were fully characterized for their particle size, zeta potential, particle morphology, drug entrapment efficiency, and in vitro drug release profile. The prepared niosomal nanocarriers exhibited nanoscale particle sizes of 165.35 ± 2.75-322.85 ± 2.75 nm. Chitosan-coated and TPP-crosslinked niosomes exhibited a slightly decreased in particle size and a switch of zeta potential from negative to positive values. In addition, high yield percentage, drug encapsulation efficiency, and drug loading values of 92.11 ± 2.07 %, 66.59 ± 6.06, and 4.65 ± 0.5 were obtained for chitosan-coated formulations, respectively. Moreover, lowering the rate of 5-FU in vitro release was achieved within 72 h by using chitosan-coated formulations. All prepared formulations revealed hemocompatible properties in hemolysis assay with less than 5 % hemolysis percentage at their higher possible concentrations (500 µM and 1 mM). The cell viability by MTT assay showed higher anticancer activity against B16F10 cancerous cells and lower cytotoxicity toward NIH3T3 normal cells than control and pure 5-FU in the studied concentration range (10-100 µM). Investigating the cell migration inhibition properties of fabricated formulations revealed similar results with in vitro cell viability assay with a higher migration inhibition rate for B16F10 cells than NIH3T3 cells, controls, and free 5-FU.

Hospital wastewater treatment using eco-friendly eugenol nanostructured lipid carriers: Formulation, optimization, and in vitro study for antibacterial and antioxidant properties.

In this study, nano-formulation has been used to tackle one of the most important environmental problems which can be considered a major threat to human health. We prepared some eco-friendly nanostructured lipid carriers (NLCs) as delivery agents to properly deliver an antibacterial agent (eugenol) into hospital wastewater in order to control bacterial growth. Eugenol-loaded nanostructured lipid carriers were prepared by hot high-speed homogenization. Then, the prepared nanocarriers were characterized using different techniques such as transmission electron microscopy, Fourier transform infrared, and dynamic scanning calorimetry. The turbidity assay and colony counting method were used to determine the ability of the prepared eugenol-loaded nanostructured lipid carriers to inhibit bacterial growth rate in the culture media and hospital wastewater, respectively. The mean size and zeta potential of NLC-eugenol were 78.12 ± 6.1 nm and -29.43 ± 2.21 mV, respectively. The results showed that the highest inhibitory effect of NLC-eugenol in culture media was seen in standard and wild Staphylococcus aureus strains (43.42% and 26.41%, respectively) with a concentration of 0.125 µM. The antibacterial activity of NLC-eugenol in sterile wastewater on wild strains of bacteria showed that the most effective concentration to reduce bacterial amounts was 0.125 µM on wild S. aureus and Enterococcus faecalis strains (38% and 33.47%, respectively) at 37°C. The NLC-eugenol with a concentration of 0.125 µM showed the greatest effect of reducing total microbial agents by 28.66% in hospital wastewater at 25°C. The highest antibacterial effect achieved using the 0.125 µM concentration is due to the egel phenomenon. Also, the mechanism of action of NLC-eugenol is cell wall destruction and eventually cell death. The results showed that NLC-eugenol with a concentration of 0.125 µM can reduce wild bacterial strains in sterilized wastewater and hospital wastewater, which can prove the great potential of the prepared eugenol-loaded nanostructured lipid carriers to control bacterial growth. PRACTITIONER POINTS: NLC is one of the safest biodegradable and environmentally friendly carriers, which is nontoxic for humans and the environment. Eugenol is a natural compound, which makes it less toxic for the environment while being toxic for bacteria. Therefore, our method has the least side effect in comparison with existing methods for wastewater treatment. The gradual release of eugenol from NLC nanoparticles can effectively control the pathogenic factors of wastewater.

Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5ß1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro. METHODS: Regorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the ß1 subunit of integrin were determined by the real-time method of RT-PCR. RESULTS: Developed Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The ß1 mRNA level of whole α5ß1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy. CONCLUSION: Results of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro.