Encapsulation, Release, and Cytotoxicity of Doxorubicin Loaded in Liposomes, Micelles, and Metal-Organic Frameworks: A Review.

Doxorubicin (DOX) is one of the most widely used anthracycline anticancer drugs due to its high efficacy and evident antitumoral activity on several cancer types. However, its effective utilization is hindered by the adverse side effects associated with its administration, the detriment to the patients' quality of life, and general toxicity to healthy fast-dividing cells. Thus, delivering DOX to the tumor site encapsulated inside nanocarrier-based systems is an area of research that has garnered colossal interest in targeted medicine. Nanoparticles can be used as vehicles for the localized delivery and release of DOX, decreasing the effects on neighboring healthy cells and providing more control over the drug's release and distribution. This review presents an overview of DOX-based nanocarrier delivery systems, covering loading methods, release rate, and the cytotoxicity of liposomal, micellar, and metal organic frameworks (MOFs) platforms.

Association of urogenital and intestinal parasitic infections with type 2 diabetes individuals: a comparative study.

BACKGROUND: Globally, urogenital and intestinal parasitosis remain significant health challenges. They are associated with rising morbidity, death, and many harmful outcomes. A little is known concerning parasitosis and type 2 diabetes mellitus. Our study planned to investigate the urogenital and intestinal parasitic infections among type 2 diabetes patients compare to non-diabetic (Control) individuals and examine the intensity of helminthiasis in both groups. METHODS: At Kosti Teaching Hospital (Sudan), 300 Urine and 300 stool samples have collected from 150 type 2 diabetes and 150 control individuals, along with the socio-demographic data using a structured questionnaire. The parasitic infections were examined by direct sedimentation technique for urine specimens. Whereas, for fecal samples, simple-direct saline, formal-ether concentration, Kato-Katz, and modified Ziehl-Neelsen techniques were used. RESULTS: Out of 150 type 2 diabetes patients studied, 31 (20.6%) and 14 (9.3%) had intestinal parasitosis and urogenital schistosomiasis, respectively. Whereas, 16 (10.6%) and 8 (5.3%) of the control group were infected, respectively. Compared to the control group, the odds of testing positive for either urogenital schistosomiasis (AOR: 2.548, 95% CI: 0.836-7.761, P = 0.100) or intestinal parasitic diseases (AOR: 2.099, 95% CI: 0.973-4.531, P = 0.059) were greater in diabetic individuals. Likewise, the intensities of helminthiasis were much higher in the diabetic patients and positively correlated with the duration of illness. The rate of urogenital schistosomiasis was also significantly different among the disease duration subcategories. CONCLUSIONS: Our study has highlighted the relationship of type 2 diabetes with urogenital and intestinal parasitic infections and enhanced our knowledge about the frequency of particular urogenital and intestinal parasites as well as the intensity of helminths infection in type 2 diabetes compared to non-diabetic individuals, which are important for further studies.

Facile Ultrasound-Triggered Release of Calcein and Doxorubicin from Iron-Based Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are promising new nanocarriers with potential use in anticancer drug delivery. However, there is a scarcity of studies on the uptake and release of guest molecules associated with MOF nanovehicles, and their mechanism is poorly understood. In this work, newly developed iron-based MOFs, namely Fe-NDC nanorods, were investigated as potential nanocarriers for calcein (as a model drug/dye) and Doxorubicin (a chemotherapeutic drug (DOX)). Calcein was successfully loaded by equilibrating its solution with the MOFs nanoparticles under constant stirring. The calcein average encapsulation efficiency achieved was 43.13%, with a corresponding capacity of 17.74 wt.%. In-vitro calcein release was then carried out at 37°C in phosphate buffer saline (PBS) using ultrasound (US) as an external trigger. MOFs released an average of 17.8% (without US), whereas they released up to 95.2% of their contents when 40-kHz US at ~1 W/cm² was applied for 10 min. The Cytotoxic drug DOX was also encapsulated in Fe-NDC, and its In-vitro release profile was determined under the same conditions. DOX encapsulation efficiency and capacity were found to be 16.10% and 13.37 wt.%, respectively. In-vitro release experiments demonstrated significant release, reaching 80% in 245 minutes, under acoustic irradiation, compared to around 6% in the absence of US. Additionally, experimental results showed that Fe-NDC nanoparticles are biocompatible even at relatively high concentrations, with an MCF-7 IC50 of 1022 g/ml. Our work provides a promising platform for anticancer drug delivery by utilizing biocompatible Fe-NDC nanoparticles and US as an external trigger mechanism.

Synthesis of Metal-Organic Framework from Iron Nitrate and 2,6-Naphthalenedicarboxylic Acid and Its Application as Drug Carrier.

Metal-organic frameworks (MOFs) are highly crystalline porous organic-inorganic materials that are comprised of metal salts and organic linkers. The common synthetic methodologies of MOFs include: solvothermal, microwave-assisted, electrochemical, mechanochemical, and sonochemical routes. The synthesized MOF particles can be characterized using several characterization techniques including: X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and other analytical techniques. Recently, MOFs have garnered increasing attention due to their potential applications in numerous areas including: catalysis, gas storage and separation, drug delivery, and others. In this research paper, a new metal-organic framework was synthesized successfully from iron nitrate and 2,6-naphthalenedicarboxylic acid (1) by means of microwave irradiation (Fe-NDC-M) and (2) solvothermally using a conventional electric oven (Fe-NDC-O). They were characterized using XRD, SEM, FTIR, energy-dispersive X-ray (EDS), thermogravimetric analysis (TGA), and N2 sorption experiments. The characterization results showed that the synthesized samples were crystals with a rod-like shape. The particle diameters ranged between 50-80 nm with a length of 300-450 nm. The BJH adsorption averagepore diameters were found to be 148.551 Å and 139.265 Å for Fe-NDC-M and Fe-NDC-O, respectively. As a result, the new Fe-NDC-MOF particles can be used as nanocarriers for anticancer drug delivery applications utilizing the enhanced permeability and retention effect.

Anti-cancer Drug Delivery Using Metal Organic Frameworks (MOFs).

Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks, anti-cancer drug delivery systems have been developed recently using nanocarriers including liposomes, micelles, polyelectrolyte capsules and others. One of the recent class of nanoparticles investigated for chemotherapeutic use are metal organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or clusters and organic ligands. MOFs are used in many applications including gas/vapor separation, gas storage, catalysis, luminescent materials, and biomedical imaging. These structures have additional features that promote their use as drug carriers in the biomedical field. First, they are nontoxic, biodegradable and have the ability to carry high loadings of the anti-neoplastic agent due to their porous nature. Also, they have well-defined crystalline structures that can be characterized by different analytical techniques and their sizes are suitable to control their in vivo drug release. This paper reviews the methods used to synthesize MOFs and their recent use as antineoplastic drug delivery carriers.

Sandflies (Diptera: Psychodidae) in a focus of visceral leishmaniasis in White Nile, Sudan.

Visceral leishmaniasis (VL) has been known to occur since the 1980s on the western bank of the White Nile River (Central Sudan), 150 km south of Khartoum, and has resulted in high mortality. The most recent outbreak of the disease in this area began in 2006. Entomological surveys were carried out during May 2008, June 2010 and May and July 2011 in the White Nile area. Sandflies were collected using Centers for Disease Control light traps and sticky oil traps in the village of Kadaba and the nearby woodland. Phlebotomus females were dissected for the presence of Leishmania promastigotes. A total of 17,387 sandflies, including six species of Phlebotomus and 10 species of Sergentomyia, were identified. The Phlebotomus species recorded were Phlebotomus orientalis, Phlebotomus papatasi, Phlebotomus bergeroti, Phlebotomus duboscqi, Phlebotomus rodhaini and Phlebotomus saevus. P. orientalis was collected in both habitats. The relative abundance of P. orientalis in the woodland habitat was higher than that recorded in the village habitat. In the woodland habitat, there was a notable increase in the relative abundance of P. orientalis during the surveys conducted in 2008 and 2010 compared to 2011. None of the 311 P. orientalis females dissected were infected with Leishmania promastigotes, although relatively high parous rates were recorded in both habitats. Based on the distribution of P. orientalis recorded in this study, this species is the most likely vector of VL in the endemic focus in the White Nile area. Further investigation is required to elucidate the seasonal abundance and distribution of the vector, as well as the transmission season of VL in both habitats so that appropriate control strategies for the vector can be designed.

Sandflies (Diptera: Psychodidae) in a focus of visceral leishmaniasis in White Nile, Sudan

Visceral leishmaniasis (VL) has been known to occur since the 1980s on the western bank of the White Nile River (Central Sudan), 150 km south of Khartoum, and has resulted in high mortality. The most recent outbreak of the disease in this area began in 2006. Entomological surveys were carried out during May 2008, June 2010 and May and July 2011 in the White Nile area. Sandflies were collected using Centers for Disease Control light traps and sticky oil traps in the village of Kadaba and the nearby woodland. Phlebotomus females were dissected for the presence of Leishmania promastigotes. A total of 17,387 sandflies, including six species of Phlebotomus and 10 species of Sergentomyia, were identified. The Phlebotomus species recorded were Phlebotomus orientalis, Phlebotomus papatasi, Phlebotomus bergeroti, Phlebotomus duboscqi, Phlebotomus rodhaini and Phlebotomus saevus. P. orientalis was collected in both habitats. The relative abundance of P. orientalis in the woodland habitat was higher than that recorded in the village habitat. In the woodland habitat, there was a notable increase in the relative abundance of P. orientalis during the surveys conducted in 2008 and 2010 compared to 2011. None of the 311 P. orientalis females dissected were infected with Leishmania promastigotes, although relatively high parous rates were recorded in both habitats. Based on the distribution of P. orientalis recorded in this study, this species is the most likely vector of VL in the endemic focus in the White Nile area. Further investigation is required to elucidate the seasonal abundance and distribution of the vector, as well as the transmission season of VL in both habitats so that appropriate control strategies for the vector can be designed.

Insecticide resistance in the sand fly, Phlebotomus papatasi from Khartoum State, Sudan.

BACKGROUND: Phlebotomus papatasi the vector of cutaneous leishmaniasis (CL) is the most widely spread sand fly in Sudan. No data has previously been collected on insecticide susceptibility and/or resistance of this vector, and a first study to establish a baseline data is reported here. METHODS: Sand flies were collected from Surogia village, (Khartoum State), Rahad Game Reserve (eastern Sudan) and White Nile area (Central Sudan) using light traps. Sand flies were reared in the Tropical Medicine Research Institute laboratory. The insecticide susceptibility status of first progeny (F1) of P. papatasi of each population was tested using WHO insecticide kits. Also, P. papatasi specimens from Surogia village and Rahad Game Reserve were assayed for activities of enzyme systems involved in insecticide resistance (acetylcholinesterase (AChE), non-specific carboxylesterases (EST), glutathione-S-transferases (GSTs) and cytochrome p450 monooxygenases (Cyt p450). RESULTS: Populations of P. papatasi from White Nile and Rahad Game Reserve were sensitive to dichlorodiphenyltrichloroethane (DDT), permethrin, malathion, and propoxur. However, the P. papatasi population from Surogia village was sensitive to DDT and permethrin but highly resistant to malathion and propoxur. Furthermore, P. papatasi of Surogia village had significantly higher insecticide detoxification enzyme activity than of those of Rahad Game Reserve. The sand fly population in Surogia displayed high AChE activity and only three specimens had elevated levels for EST and GST. CONCLUSIONS: The study provided evidence for malathion and propoxur resistance in the sand fly population of Surogia village, which probably resulted from anti-malarial control activities carried out in the area during the past 50 years.