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Plants synthesize large amount of useful and complex products which have no obvious metabolic and growth functions. These complex materials are said to be as secondary metabolites—phytochemicals which are plants active compounds possessing the potential to inhibit diseases. The purpose of the recent study was to investigate the pharmaceutical values of the flowers of Taraxacum officinale, for antimicrobial, anti-pellicle and anti-biofilm properties. Metanolic extracts with chloroform and n-hexane fractions against selected different bacterial (E.coli, P.aeruginosa, S.aureus, S.typhi) and fungal (F.oxysporum, A.niger, A.alternata, A.Terreus) strains were tested and GC-MS, FTIR and HPLC techniques, for detection of various secondary metabolites which are responsible for these activities, were performed. In antimicrobial assay, the result of the methanolic extract and fractions of the flowers was found to be effective against the tested bacterial and fungal strains. The GC-MS and FTIR analysis of chloroform fractions of T. officinale flowers reported the presence of a wide range of phytochemicals and secondery metabolites liable for the biological activities that can be purified in future for the synthesis of noval improved and valuable pharmaceutical products.

Background: Since the beginning of medical history, plants have been exemplary sources of a variety of pharmacological compounds that are still used in modern medication. Respiratory infections are a serious and persistent global health problem, most acute and chronic respiratory infections are caused by viruses, whose ability to mutate rapidly may result in epidemics and pandemics, as seen recently with MERS-COV (2012) and SARS-COV-2 (2019), the latter causing coronavirus disease 2019 (COVID-19). Methods: This study aims to highlight the tremendous benefits of plants that have been widely used as dietary supplements or traditional treatment for various respiratory infections, with a focus on the most effective constituents and studies that revealed their activities against COVID-19. Results: Several traditional plants and their phytoconstituents have shown activity against respiratory viruses, including SARS-COV-2. The presented plants are Nigella sativa, Punica granatum, Panax ginseng, Withania somnifera, Glycyrrhiza glabra, Curcuma longa, Zingiber officinale, Camellia sinensis, Echinacea purpurea, Strobilanthes cusia, Stephania tetrandra, and genus Sambucus. Conclusion: The data discussed in this review can encourage carrying out in-vivo studies that may help in the discovery of herbal leads that can be feasibly used to alleviate, prevent or treat COVID-19 infection.

Nanocomposite films have been prepared from chitosan, cinnamaldehyde, Nigella sativa or blackseed oil, and silver nanoparticles (NPs) biosynthesized in Azadirachta indica or neem leaves’ extract. The methodology involved simple blending of components through “green chemistry” route. The films obtained were soft and foldable. The morphology by scanning electron microscopy confirmed the inclusion of NPs in the films. Microbial penetration study demonstrated that the films offered good resistance to secondary bacterial infection. The antibacterial study against Staphylococcus aureus (ATCC 29213) and E. coli (ATCC 25922) indicated moderate antibacterial behavior of the films. The swelling behavior in water, phosphate buffer saline, and simulated wound fluid was found to be appropriate for use as wound dressings. The films were biodegradable in soil and showed good thermal stability up to 200°C.

Objectives. The aim of this study is to assess the effect of open apex on working length (WL) determination with aid of cone-beam computed tomography (CBCT) and electronic apex locators (EALs). Methods. Thirty-two extracted human mandibular premolars were selected, and apical 5 mm was removed. Root canals were prepared from the apical to the coronal direction of the canal using peeso reamers up to size 5 (retrograde) to simulate open apex. The samples were analyzed by CBCT, and WL was established (CWL) by a radiologist. An endodontist prepared the access cavities, and visual working length (VWL) was recorded. The samples were embedded in a freshly mixed alginate mould up to cementoenamel junction. Each root canal length was measured with two different EALs—Root ZX mini and i Root. The measurements were repeated 3 times by using a digital caliper, and the mean was recorded by the endodontist who was blinded to the results of the CWL. The recorded data was statistically analyzed using the SPSS software. Results. The results of this study showed statistically significant difference between VWL and i Root, CWL and i Root, and Root ZX mini and i Root ( p < 0.05 ). Amongst EALs, a superior accuracy was noted for Root ZX mini than as compared to i Root. However, no statistically significant difference was seen between Root ZX mini and CWL ( p > 0.05 ). Conclusion. The present study showed that CWL is as accurate and reliable as VWL which is the gold standard. Amongst EALs, Root ZX mini performed more accurately than i Root. Preexisting CBCT scans should be used as an advantage in determining WL.

Various endodontic interventions often lead to iatrogenic damage to the inferior alveolar nerve present in the inferior alveolar canal (IAC). The purpose of the present study was to analyze the relationships of IAC with the root apices of mandibular teeth and with the mandibular cortical plates. Materials: 116 cone beam computed tomography (CBCT) scans were examined and the shortest distance of IAC with the root apices of mandibular canines, premolars and molars, and with cortical plates was analyzed. The data were statistically analyzed using SPSS. Results: The shortest mean distance between IAC and lingual cortical plate (LCP) was found in the third molar area, and between IAC and buccal cortical plate (BCP) in the second premolar area. A high incidence of 60% direct communication (DC) was present in mandibular second molars; 38% in mandibular third molars; 13% in mandibular second premolars; 12% in mandibular first molars; and 1% in mandibular first premolars. Conclusion: Anteriorly, IAC was found to be significantly present in close approximation to the roots of mandibular canines. Posteriorly, IAC was found to be in significant proximity to the distal roots of mandibular second molars.

Nanotechnology has brought about the advent of personalized medicine in the era of targeted therapeutic strategies for cancer therapy. The ability to exploit tumor features for therapeutic gain has made it possible to manufacture more effective nanomedicines for cancer treatment. However, known obstacles, including the inability to overcome pathophysiological barriers of tumors, have impeded disease management. In spite of this, recent efforts have been made to develop more functionalized nanosystems that utilize the active-targeting approach. This article reviews the FDA-approved cancer drug delivery systems in the general framework of personalized nanomedicine. We discuss the latest efforts in the development of functionalized nano-systems, and summarize relevant ongoing preclinical and clinical trials.

One of the longstanding issues limiting the use of chemotherapeutic agents is the lack of tumor specificity, which leads to systemic toxicity. Therefore, various targeted nanocarriers have been developed to concentrate the cytotoxic drug agents at tumor regions to avoid uptake by normal healthy tissues. Previous studies from our laboratory have demonstrated that cell membrane lipid-extracted nanoliposomes (CLENs) are capable of selective targeting compared to nanoliposomes consisting of mainly conventional lipid materials. Also, CLENs were relatively nontoxic when employed at concentrations traditionally used to evaluate nanoparticles in vitro. However, parameters such as lipid composition, size, and surface charge all have a direct impact on liposomal cellular uptake. In this study, we prepared different CLENs different molar ratios of natural and cellular-derived lipids extracted directly from breast cancer cells (4T1), cholesterol, and DPPE-PEG-5000. The formulations were used to investigate the mechanisms of CLENs uptake and determine the underlying mechanisms regulating cellular entry. In the study, CLENs were used to evaluate cytotoxicity and cellular uptake for both target and off-target cell populations. CLENs containing cholesterol and DPPE-PEG-5000 (70/25/5) were able to retain doxorubicin in relevant therapeutic concentrations. CLEN formulations were able to exert selective cytotoxic drug effects against different target breast cancer cells in vitro. 4T1 CLENs containing cholesterol and DPPE-PEG-5000 (70/25/5) demonstrated greater binding to 4T1 (target) cells compared to CLENs prepared using 4T1 lipid extracts alone. The binding was not only temperature- and time-dependent, but also composition- and cell type-dependent. Off-target effect studies showed that 4T1 CLENs were taken up minimally by off-target cells (including normal breast fibroblasts and normal myocytes), compared to controls. Our studies collectively support the use of lipid extracts derived from target cells for selective drug targeting and enhanced cytotoxicity. Future studies will explore underlying mechanisms of cellular entry and cardioprotective function. Citation Format: Hanan M. Alharbi, Robert B. Campbell. An evaluation of breast cancer cellular membrane lipid-extracted nanoliposomes (CLENs) in relation to formulation design, stability, mechanism of cellular entry and cardioprotective function in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4666.

Background: Every year more deaths are attributed to lung cancer compared to colon, prostate, and breast cancers combined. Lung cancer is typically diagnosed at late stages, and has demonstrated poor treatment outcomes due to acquired drug resistance. Unfortunately, as one method is introduced to overcome drug resistance a new mechanism can arise. In an effort to overcome drug resistance lipid extracts (LE) were derived from target cells, and the ingredients were used to develop nanoliposomes that would selectively target a desired cell population compared to controls. The early studies were designed to demonstrate the use of CLENs (cellular membrane lipid-extracted nanoliposomes) for the targeting of lung cancer. Experimental Procedures: CLENs were initially prepared using various ratios of LE/DOPC/Chol/PEG by thin film evaporation. Particle size and zeta potential values were determined for all preparations of CLENs (with and without drug). CLENs were evaluated for selectivity for target compared to control cells. Cytotoxicity studies were performed on various doxorubicin hydrochloride-loaded CLENs using a cell model of lung cancer (ChagGo-K-1). For cellular uptake studies ChaGo-K-1 cells were seeded at 10,000 cells/mL in a 48-well plate and allowed to incubate for 24 hours prior to cell studies. A fluorescence microplate reader was used to determine fluorescence intensity values for the two studies. Results: ChaGo-K-1 CLENs demonstrated an average particle size of 206+/-2 nm and zeta-potential of -21+/-3 mV, illustrating favorable characteristics for drug delivery and interstitial drug targeting. The cellular uptake studies suggested that ChaGo-K-1 CLENs were selective for ChaGo-K-1 cells in vitro, when compared to all other control varieties of CLENs. Drug-loaded ChaGo-K-1 CLENs displayed significant cytotoxicity against ChaGo-K-1 cells compared to control cells. Fluorescence microscopy revealed association of ChagGo-K-1 CLENs with target cells. Conclusions: Based on promising early finding CLENs may represent a relatively tumor specific drug delivery system that can be used to overcome drug resistance, improve efficacy, and to limit off-target drug effects. Preclinical studies will investigate whether the relative selectivity and cytotoxicity observed against lung cancer cells in vitro translates to favorable tumor uptake and efficacy in vivo. Citation Format: Jasmine King, Aarohi Bhatt, Drew Goodrich, Thomas Preteroti, Hanan Alharbi, Robert Campbell. Development and in vitro evaluation of cell membrane lipid-extracted nanoliposomes for lung cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3876.

Background: Liposome-encapsulated doxorubicin has proven to be an effective drug delivery method to cancer cells. Lipid extracts derived from human prostate cancer cells along with conventional components were employed to develop cell membrane lipid-extracted nanoliposomes (CLENs) for prostate cancer treatment. In an effort to balance efficiency of drug loading with cellular targeting efficiency we report on physicochemical characteristics (i.e., particle size, zeta potential, drug loading efficiency) and cellular uptake studies. Methods: Five preparations of CLENS were prepared consisting of variable concentrations of DOPC and CRL-1740 lipid extract material varying as a function of optimized fixed ratios of conventional components (Cholesterol and DSPE-PEG5000). The controls used to investigate the effect of the different components on drug incorporation efficiency were preparations of DOPC (100%) and CRL-1740 (100%). Doxorubicin hydrochloride (5 mol%) was employed during the preparation of all formulations. Samples were readily prepared by thin film evaporation. For cellular uptake studies CRL-1740 cells were seeded at 1 x 104 mL in 48-well plate and incubated for 24 hours prior to use. The cells were next exposed to various amounts of rhodamine labeled CLENS for 24 hrs. Cellular uptake was determined using fluorescence intensity values determined by a fluorescence microplate reader. Fluorescence microscopy supplement cellular uptake studies. Results: The DOPC drug-loaded liposome preparation consistently achieved the lowest percent of drug incorporation. Likewise, 100% CRL-1740 CLENs demonstrated a significant degree of formulation instability, resulting in a relatively low percent of drug incorporation compared to preparations that consisted of lipid extract and conventional components. The finding were supported by values determined for zeta potential and particle size. Cellular uptake studies also favored the preparations that consisted of lipid extract material and conventional components compared to each alone. The results collectively support the importance of balancing lipid extract material derived from prostate cancer target cells with cholesterol and DSPE-PEG5000 for formulation development and cellular uptake. Conclusion: We formulated seven preparations of CLENS as part of the drug platform. The most promising candidates were determined following completion of the study. Future studies should evaluate the cytotoxicity and safety profile of the most promising formulations vivo. Citation Format: Abubker Omaer, Ali Alqarni, Carlos Randulfe, Hanan Alharbi, Robert Campbell. Formulating a cell membrane lipid-extracted nanoliposome (CLENS) drug platform for the treatment of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3881.

Breast cancer is a major cause of cancer death in women worldwide. Breast cancer is a heterogeneous disease characterized by variant pathological features, disparate responses to therapeutics, and substantial differences in patient's long-term survival. The use of drug delivery systems such as liposomes can favorably alter the pharmacokinetic and biodistribution profile of commonly used drugs used to treat breast cancer disease. An important feature of a drug delivery system is its ability to recognize and selectively target tumor cells with relatively high affinity when compared to healthy tissues. For this reason, the goal of this study was to develop a novel nanoliposome system that would target tumor cells to a significantly greater extent when compared to more conventional liposome systems. In this study, natural lipids extracted directly from breast cancer cells were used to prepare cellular lipid-extracted nanoliposomes (CLENs). The rationale is that an array of different lipids with a unique composition profile would represent a more relevant source of lipid material when compared to more traditional methods of liposome preparation. We therefore investigated whether the inclusion of extracted lipids derived from breast cancer cells would improve the selective uptake of liposomes by breast cancer cells, and related formulation features. To achieve these goals, three breast cancer cell lines were used (4T1, BT-20, and SK-BR-3), a normal breast fibroblast (CRL-2089), and an ovarian cancer cell line (SK-OV-3- used as a negative control). The size of CLENs fell within the size range of 120- 203 nm and possessed a negatively-charged liposome surface charge potential (ranging between -10.97 and -20.97 mV). The nanoliposomes were also non-toxic to cells within the concentration range evaluated (up to 1μmol). Furthermore, without exception, the cellular uptake of CLENs was greatest when the extracted material used to prepare CLENs was the same as the target cell from which the lipids were extracted. In addition, when the breast cancer cell lines (4T1, SK-BR-3 and BT-20) were used to prepare CLENs, SK-OV-3 and CRL-2089 cell lines took up CLENs to a lesser extent, suggesting a more selective and differential cellular uptake. In conclusion, the novel nanoliposome platform represents a promising drug delivery alternative to more conventional nano drug delivery systems. Additional formulation studies are currently underway. Citation Format: Hanan M. Alharbi, Robert B. Campbell. Employing a unique panel of breast cancer cellular lipids extracts in the development of a novel nanoliposome drug platform. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5513. doi:10.1158/1538-7445.AM2015-5513