Development of Gefitinib-Loaded Solid Lipid Nanoparticles for the Treatment of Breast Cancer: Physicochemical Evaluation, Stability, and Anticancer Activity in Breast Cancer (MCF-7) Cells.

In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.

Development and Evaluation of Nanoformulations Containing Timur Oil and Rosemary Oil for Treatment of Topical Fungal Infections.

The pervasiveness of fungal infections is an issue for skin health globally, and there are a reported 40 million cases in developed and developing countries. Novel drug delivery systems provide better therapeutic efficacy over conventional drug therapy due to their lower side effects and toxicity. Furthermore, combinations of essential oils can represent alternative therapies for fungal infections that are resistant to synthetic drugs. This study is aimed at developing Timur oil into a nanoemulgel and evaluating its antifungal effects. The development of the formulation involved the preparation of a nanoemulsion by the titration method, followed by its evaluation for various physicochemical properties. The antifungal activity of the nanoemulgel against Candida albicans was evaluated. The zone of inhibition was determined using the disk diffusion method. The results show that the developed nanoemulgel has a particle size of 139 ± 6.11 nm, a PDI of 0.309, and a zeta potential of -19.12 ± 2.73 mV. An in vitro drug release study showed a sustained release of 70 ± 0.289% of the drug over a period of 24 h. The % drug permeation across the skin was found to be 79.11 ± 0.319% over 24 h. However, the amount of drug retained in the skin was 56.45 µg/g. The flux for the nanoemulgel was found to be 94.947 µg/cm2/h, indicating a better permeability profile. The nanoemulgel formulation showed a zone of inhibition of 15 ± 2.45 mm, whereas the 1% ketoconazole cream (marketed preparation) exhibited a zone of inhibition of 13 ± 2.13 mm. The results of this study suggest that developed nanoemulgel containing Timur oil and rosemary oil has the potential to be used for treating topical fungal infections caused by Candida albicans.

Carduus edelbergii Rech. f. Mediated Fabrication of Gold Nanoparticles; Characterization and Evaluation of Antimicrobial, Antioxidant and Antidiabetic Potency of the Synthesized AuNPs.

Background: Due to the high expense, less effectiveness and more side effects of available synthetic medicine, the researchers and communities are focusing on phyto-based natural bioactive compounds, which are considered safer for the treatment of syndromes and chronic diseases. Aim: The current project was aimed to determine the phytochemicals constituents available in the aerial parts of methanol extract of Carduus edelbergii via GC-MS, fabrication of AuNPs mediated with the mentioned extract; characterization and evaluation of antimicrobial, antioxidant and antidiabetic potency of the synthesized AuNPs. Methods: Confirmation of green synthesis of AuNPs, functional groups responsible for the reduction in Au+, size and crystallinity, morphology and quantity of gold (Au) were carried out by Ultraviolet-Visible (UV-Vis) spectroscopy, Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and dispersive X-ray (EDX), respectively, whereas in vitro antioxidant characteristics were assessed by DPPH and ABTS assays. Wistar albino rats were used to test the anti-diabetic properties of the methanol extract and AuNPs. Results: GC-MS revealed that the diluted methanol extract of Carduus edelbergii consists of about 19 chemical constituents. Among the identified compounds, the 13-Docosenoic acid, methyl ester, (Z)­has the highest concentration (38.16%), followed by 9-Octadecenoic acid, methyl ester, (E)­(15.72%) and n-Hexadecanoic acid (15.07%). Methanol extract and its fabricated nanoparticles showed significant antioxidant and antimicrobial activities. In vivo antidiabetic study revealed a noteworthy (p < 0.05) decline in body weight and HDL and elevated concentration of blood glucose, bilirubin, creatinine, urea, triglyceride, VLDL, LDL, ALP, ALT and AST in diabetic control. The said changes were recovered significantly (p < 0.05) by treatment of diabetic rats with methanol extract (150 and 300 mg/Kg BW) and AuNPs of Carduus edelbergii (5 and 10 mg/Kg BW). Conclusion: The green synthesized AuNPs exhibit significant antioxidant, antimicrobial and antidiabetic characteristics.

A New Clinical Sign In Meningitis-Jamil's Sign.

BACKGROUND: This study explored a new clinical sign in meningitis: neck stiffness in lateral position, also known as Jamil's sign. METHODS: A patient was placed in the left lateral position. The examiner held the patient's occiput with his left hand and the chin with his right hand. Then, the examiner performed a manoeuvre by fully extending and then fully flexing the neck. By doing so, the examiner was able to get ample time and range of movement to judge the tone. The tone was assessed during flexion and extension. If the examiner felt resistance, rigidity, or stiffness while performing this manoeuvre, Jamil's sign was present. Otherwise, it was supple, and Jamil's sign was absent. RESULTS: Of the 419 patients, Jamil's sign was present in 362 patients and absent in 57 patients. Upon lumbar puncture, 361 patients had meningitis, and 58 patients did not have meningitis. Among patients with meningitis, Jamil's sign was present in 357 patients and absent in four patients. Jamil's sign had a sensitivity of 98.89% and a specificity of 91.38. CONCLUSIONS: Due to its high sensitivity and specificity for the diagnosis of meningitis, Jamil's sign obviates the need for unnecessary lumbar puncture, which is performed in doubtful situations of neck stiffness in the supine position.

Arthralgia In A Young Patient: Presentation Of Lofgren Syndrome.

Lofgren syndrome an acute form of sarcoidosis constitutes erythema nodosum, bilateral hilar adenopathy and arthralgia or arthritis. Here we present a case of a 28 years old young male patient who is a shopkeeper and farmer by profession admitted to inpatient department with chief complaints of bilateral painful nodules on his shins, low grade fever and pain multiple joints on both sides of the body. Suspicion of the Lofgren syndrome was made upon initial evaluation and patient was admitted to inpatient care facility for necessary comprehensive workup. Radiological findings were consistent with bilateral hilar lymphadenopathy and patient was diagnosed with Lofgren syndrome. Patient was started on non-steroidal inflammatory drugs (NSAIDs) with close observation for improvement in response to treatment. After one weak of treatment in hospital, patient was discharged home when his symptoms started to resolve.

Biogenic Synthesis of Silver Nanoparticles Using Phagnalon niveum and Its In Vivo Anti-Diabetic Effect against Alloxan-Induced Diabetic Wistar Rats.

Background: Type-2 diabetes mellitus (T2DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective and green synthesised nanoparticles (NPs) as a medicinal therapy in the treatment of T2DM is an attractive option. Aim: The present study aimed to evaluate the anti-diabetic potential of the phyto-synthesised silver nanoparticles (AgNPs) obtained from Phagnalon niveum plant methanolic extract. Methods: The green synthesised AgNPs made from Phagnalon niveum plant methanolic extract were analysed by Ultraviolet-Visible (UV-Vis) spectroscopy, and the functional groups involved in the reduction of the silver ions (Ag+) were characterised by Fourier Transform Infrared (FTIR) spectroscopy. The size and crystallinity were assessed via X-ray Diffraction (XRD). The morphology of AgNPs was confirmed using Scanning Electron Microscopy (SEM). The amount of silver (Ag) was estimated via energy dispersive X-ray (EDX) analysis. An intraperitoneal injection of 200 mg alloxan per kg albino Wistar rats' body weight, at eight weeks old and weighing 140-150 g, was used to induce diabetes mellitus (N = 25; n = 5/group). Group C: untreated normal control rats that only received distilled water, group DAC: diabetic control rats that received alloxan 200 mg/Kg body weight, DG: diabetic rats treated with glibenclamide at 0.5 mg/kg body weight, DE: diabetic rats that received methanolic P. niveum extract at 10 mg/Kg body weight, and DAgNPs: diabetic rates that received AgNPs synthesised from P. niveum at 10 mg/kg body weight. The blood glucose levels were monitored on days 0, 7, and 14, while lipid, liver, and kidney profiles were checked after dissection at the end of treatment (day 21). On the final day of the period study (day 21), an oral glucose tolerance test was carried out by administering orally 2 g/kg body weight of glucose to the respective groups, and the blood glucose level was checked. A fasting glucose level was measured using a glucometer. Urine samples were collected from each animal and analysed using lab-made assay kits for glucose, bilirubin, pH, leukocytes, and nitrite, among other factors. For statistical analyses, a one-way ANOVA and Dunnett's test were applied. Results: The green-mediated synthesis of AgNPs using P. niveum methanolic extract produced spherical and mono-dispersed NPs with a size ranging from 12 to 28 nm (average: 21 nm). Importantly, a significant reduction of blood glucose levels and an increase in body weight, as well as a remarkable improvement in lipid, liver, and kidney profiles, were noticed. Conclusions: The biosynthesised AgNPs significantly improved the abnormalities in body weight, urine, and serum levels, indicating that it is a promising anti-diabetic agent.

Development and evaluation of PLGA polymer based nanoparticles of quercetin.

Quercetin is the most abundant antioxidant found in the human diet. Low aqueous solubility of quercetin limits its bioavailability and hence therapeutic effects. Therefore, the aim of the present study was to develop a poly lactide-co-glycolic acid (PLGA) polymer based nanoparticles of quercetin with a view to improve its aqueous solubility and examine the effect on its antioxidant and diuretic properties. Nanoparticles of quercetin were developed by single emulsion-solvent evaporation technique and evaluated in vitro for differential scanning calorimetry (DSC), Fourier transforms infra-red (FTIR) spectroscopy, particle size, polydispersity index and drug entrapment efficiency. Among the five different formulations (F1, F2, F3, F4 and F5), F2 and F3 were optimized with an average particle size of 189nm and 186nm and high entrapment values of 86.48%, 83.71%, respectively. SEM images of confirmed that prepared nanoparticles were spherical in shape with a smooth surface. In vitro release and anti-oxidant activity confirmed significant results. Furthermore, its in vivo diuretic activity was much better as compared to pure quercetin. The overall results suggest that PLGA polymer based nanoparticle could be a potential option for quercetin delivery.

Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats.

OBJECTIVE: Insulin is a hormone used in the treatment of diabetes mellitus. Multiple injections of insulin every day may causes pain, allergic reactions at injection site, which lead to low patient compliance. The aim of this work was to develop and evaluate an efficient solid lipid nanoparticle (SLN) carrier for oral delivery of insulin. METHODS: SLNs were prepared by double emulsion solvent evaporation (w/o/w) technique, employing glyceryltrimyristate (Dynasan 114) as lipid phase and soy lecithin and polyvinyl alcohol as primary and secondary emulsifier, respectively, and evaluated in vitro for particle size, polydispersity index (PDI) and drug entrapment. RESULTS: Among the eight different developed formulae (F1-F8), F7 showed an average particle size (99 nm), PDI (0.021), high entrapment of drug (56.5%). The optimized formulation (F7) was further evaluated by FT-IR, DSC, XRD, in vitro release, permeation, stability, bioavailability and pharmacological studies. Insulin-loaded SLNs showed better protection from gastrointestinal environment as evident from the relative bioavailability, which was enhanced five times as compared to the insulin solution. A significant enhancement of relative bioavailability of insulin was observed, i.e. approximately five times of pure insulin solution when loaded in SLN (8.26% versus 1.7% only).

Enhanced antibacterial effects of clove essential oil by nanoemulsion.

The aim of present study was to develop and evaluate nanoemulsion formulations of clove essential oil (CEO) for its antibacterial effects in comparison with pure CEO and standard amikacin antibiotic (positive control). Different nanoemulsions of CEO were developed by aqueous phase titration method via construction of pseudo-ternary phase diagrams and investigated for thermodynamic stability and self-nanoemulsification tests. Selected formulations (F1-F5) were characterized for droplet size distribution, viscosity, zeta potential, transmittance and surface morphology. Based on lowest droplet size (29.1 nm), lowest PI (0.026), lowest viscosity (34.6 cp), optimal zeta potential (-31.4 mV), highest transmittance (99.4 %) and lowest concentration of Triacetin (8 % w/w), CEO nanoemulsion F1 (containing 1 % w/w of CEO, 8 % w/w of Triacetin, 15 % w/w of Tween-80, 15 % w/w of Labrasol and 61 % w/w of water) was subjected to antibacterial studies in comparison with pure oil and standard amikacin. The antibacterial effects of F1 were found to be superior over pure oil against all bacterial strains investigated. However, the antibacterial effects of F1 were highly comparable with standard amikacin against all bacterial strains. The minimum inhibitory concentrations (MICs) of F1 were observed in the range of 0.075-0.300 % w/w as compared to pure oil (MICs 0.130-0.500 % w/w) and standard amikacin (MICs 2-16 µg/ml). These results indicated the potential of nanoemulsions for enhancing the therapeutic efficacy of natural bioactive ingredients such as CEO.

Seasonal variations of vivax and falciparum malaria: an observation at a tertiary care hospital.

BACKGROUND: Malaria is a major public health problem in the malaria endemic zones of the world. Various factors influence the prevalence of malaria. This study was conducted to determine the variation in frequency of Plasmodium vivax and Plasmodium falciparum malaria in different seasons of the year in Khyber Teaching Hospital, Peshawar. METHODS: A total of 411 patients were included in the study. All these febrile patients were reported to have trophozoites of either Plasmodium vivax or Plasmodium falciparum malaria on Giemsa stained thick and thin smears. The frequency of vivax and falciparum malaria was worked out and statistically analysed for different season of the year. The study was carried out from 2nd Jan 2004 till 31st December 2008. RESULTS: Out of total 411 diagnosed malaria cases, total 134 (32.60%) presented in the autumn season (vivax = 33.58%, and falciparum = 66.42%), 37 (9%) in winter season (vivax = 32.4%, and falciparum = 67.6%), 76 (18.49%) in spring season (vivax = 93.4% and falciparum 6.6%) and 164 (39.90%) in summer season (vivax = 89.6, and falciparum = 10.4%). The malaria showed a highly significant pattern in different seasons of the year (p = 0.00) in a way that Plasmodium falciparum malaria reached its highest frequency in autumn and winter seasons while Plasmodium vivax malaria reached its peak frequency in spring and summer seasons. CONCLUSION: There was highly significant seasonal variation of vivax and falciparum malaria. There is arrival of Plasmodium falciparum in autumn which peaks in winter followed by arrival of Plasmodium vivax in spring till the end of summer.