Arsenic trioxide and Erlotinib loaded in RGD-modified nanoliposomes for targeted combination delivery to PC3 and PANC-1 cell lines.

During the past few years, advances in drag delivery have provided many opportunities in the treatment of various diseases and cancer. Arsenic trioxide (ATO) and Erlotinib (Erlo) are two drugs, approved by the United States Food and Drug Administration to treat cancer, but their use is limited in terms of the toxicity of ATO and the low solubility of Erlo. This study aimed to prepare arginine-glycine-aspartic acid (RGD)-decorated nanoliposomes (NLPs) containing Erlo and ATO (NLPs-ATO-Erlo-RGD) to increase the solubility and reduce the toxicity of Erlo and ATO for cancer treatment. The results of transmission electron microscopy and dynamic light scattering showed that NLPs were synthesized uniformly, with spherical shape morphology and particle sizes between 140 and 160 nm. High-performance liquid chromatography and ICP-MS results showed that about 90% of the drug was loaded in the NLPs. In comparison with NLPs-ATO-Erlo, NLPs-ATO-Erlo-RGD demonstrated considerable toxicity against the αvß3 overexpressing PC3 cell line in the MTT experiment. It had no effect on the PANC-1 cell line. In addition, apoptosis assays using Annexin V/PI demonstrated that NLPs-ATO-Erlo-RGD generated the highest apoptotic rates in PC3 cells when compared with NLPs-ATO-Erlo and the combination of free ATO and Erlo. Furthermore, treatment with NLPs-ATO-Erlo-RGD in (p < 0.05) PC3 cell line significantly reduced EGFR level. It is concluded NLPs-ATO-Erlo-RGD as a novel drug delivery system may be a promising platform for the treatment of cancer.

Design, synthesis, spectroscopic characterization, in vitro tyrosinase inhibition, antioxidant evaluation, in silico and kinetic studies of substituted indole-carbohydrazides.

In the current study, twenty-five indole-carbohydrazide derivatives linked to different aryl substitutions were rationally designed and synthesized. The structures of all derivatives were confirmed using different spectroscopic techniques including 1H NMR, 13C NMR, Mass spectrometry, and elemental analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC50 values in the range of 0.070 to > 100 µM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC50 = 0.070 µM), 8f (R = 4-OH, IC50 = 0.072 µM), and 19e (IC50 = 0.19 µM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited that compounds 4f, 8f, and 19e are mixed-type inhibitors. Furthermore, toxicity and cell-based anti-melanogenesis assessments were performed on the most potent derivatives and it was shown that 4f, 8f, and 19e had no toxicity at 8 µM and reduced the percent of melanin content to 68.43, 72.61, 73.47 at 8 µM, respectively. In silico analyses of absorption, distribution, metabolism, and excretion (ADME) profile of synthesized compounds showed that these molecules followed drug-likeness rules and acceptable predictive ADMET features. Results of the docking study were almost in line with biological results with ChemPLP values of 53.56 to 79.33. Also, the docking study showed the critical interactions of potent inhibitors with the active site of the enzyme which affects the potency of the synthesized hybrids. Based on molecular dynamic simulations, compound 4f exhibited pronounced interaction with the critical residues of the tyrosinase active site so that the indole ring participated in H-bond interaction with Gly281 and 4-hydroxy benzylidene recorded another H-bond interaction with Asp289 plus hydrophobic interactions with Phe292. Hydrazide linker also exhibited three H-bond interactions with His263 and Gly281.

Overview, consequences, and strategies for overcoming matrix effects in LC-MS analysis: a critical review.

The high-performance liquid chromatography-mass spectrometry (LC-MS) technique is widely applied to routine analysis in many matrices. Despite the enormous application of LC/MS, this technique is subjected to drawbacks called matrix effects (MEs) that could lead to ion suppression or ion enhancement. This phenomenon can exert a deleterious impact on the ionization efficacy of an analyte and subsequently on the important method performance parameters. LC-MS susceptibility to MEs is the main challenge of this technique in the analysis of complex matrices such as biological and food samples. Nowadays, the assessment, estimation, and overcoming of the MEs before developing a method is mandatory in any analysis. Two main approaches including the post-column infusion and post-extraction spike are proposed to determine the degree of MEs. Different strategies can be adopted to reduce or eliminate MEs depending on the complexity of the matrix. This could be done by improving extraction and clean-up methods, changing the type of ionization employed, optimization of liquid chromatography conditions, and using corrective calibration methods. This review article will provide an overview of the MEs as the Achilles heel of the LC-MS technique, the causes of ME occurrence, their consequences, and systemic approaches towards overcoming MEs during LC-MS-based multi-analyte procedures.

LC-ESI-QTOF-MS/MS characterization of phenolic compounds from Prosopis farcta (Banks & Sol.) J.F.Macbr. and their potential antioxidant activities.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.

Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease.

PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of ß-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population. METHODS: In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study. RESULTS: On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06-103.18 L), terminal half-life (T1/2) (4.51; 2.67-8.88 h) and decreased clearance (6.52; 4.43-10.16 L/h) have been shown. CONCLUSION: In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target. RETROSPECTIVELY REGISTERED: The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5.

Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis.

PURPOSE: Invasive aspergillosis is a prevalent fungal disease, especially in Asian countries with a high mortality rate. Voriconazole (VRZ) is the first choice for invasive aspergillosis treatment. Plasma concentration of this drug is unpredictable and varies among individuals. This variability is influenced by many factors leading to clinical implication. Therapeutic drug monitoring (TDM) may have a crucial role in the patients' treatment process. The HPLC method provides sufficient specificity and sensitivity for plasma VRZ concentration determination for TDM purposes of this drug. METHODS: Patients who initiated oral or intravenous VRZ for invasive aspergillosis were enrolled in this study. Demographic characteristics and clinical data, outcome, and adverse effects were documented. For each patient, the plasma sample was collected under steady-state condition and analyzed using a validated HPLC method. RESULTS: A total of 22 measurements were performed. Fifty percent of patients were out of the therapeutic range. From them, 27.27% and 22.73% were in subtherapeutic and supratherapeutic ranges (<1 µg/mL and >5.5 µg/mL), respectively. There was a significant correlation between VRZ plasma concentration and treatment outcomes (P=0.022). Treatment failure was five times higher than treatment success in those in the subtherapeutic range. Adverse effects were observed more frequently in patients with supratherapeutic concentrations compared to those with non-supratherapeutic levels. Furthermore, the mortality rate in patients experiencing treatment failure was 2.17 times higher than those with treatment success. CONCLUSIONS: TDM of VRZ plays an important role in better evaluation of efficacy and toxicity during treatment. Therefore, determination of the drug level may be of clinical significance.

Conformational change and GTPase activity of human tubulin: A comparative study on Alzheimer's disease and healthy brain.

In Alzheimer's disease (AD), the most common form of dementia, microtubules (MTs) play a pivotal role through their highly dynamic structure and instability. They mediate axonal transport that is crucial to synaptic viability. MT assembly, dynamic instability and stabilization are modulated by tau proteins, whose detachment initiates MT disintegration. Albeit extensive research, the role of GTPase activity in molecular mechanism of stability remains controversial. We hypothesized that GTPase activity is altered in AD leading to microtubule dynamic dysfunction and ultimately to neuronal death. In this paper, fresh tubulin was purified by chromatography from normal young adult, normal aged, and Alzheimer's brain tissues. Polymerization pattern, assembly kinetics and dynamics, critical concentration, GTPase activity, interaction with tau, intermolecular geometry, and conformational changes were explored via Förster Resonance Energy Transfer (FRET) and various spectroscopy methods. Results showed slower MT assembly process in samples from the brains of people with AD compared with normal young and aged brains. This observation was characterized by prolonged lag phase and increased critical and inactive concentration of tubulin. In addition, the GTPase activity in samples from AD brains was significantly higher than in both normal young and normal aged samples, concurrent with profound conformational changes and contracted intermolecular MT-tau distances as revealed by FRET. These alterations were partially restored in the presence of a microtubule stabilizer, paclitaxel. We proposed that alterations of both tubulin function and GTPase activity may be involved in the molecular neuropathogenesis of AD, thus providing new avenues for therapeutic approaches.

High-performance thin-layer chromatography fingerprinting, total phenolic and total flavonoid contents and anti-platelet-aggregation activities of Prosopis farcta extracts.

Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.

Trastuzumab-monomethyl auristatin E conjugate exhibits potent cytotoxic activity in vitro against HER2-positive human breast cancer.

Targeted therapy using specific monoclonal antibodies (mAbs) conjugated to chemotherapeutic agents or toxins has become one of the top priorities in cancer therapy. Antibody-drug conjugates (ADCs) are emerging as a promising strategy for cancer-targeted therapy. In this study, trastuzumab, a humanized monoclonal anti-HER2 antibody, was reduced by dithiothreitol and conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a valine-citrulline peptide linker (trastuzumab-MC-Val-Cit-PABC-MMAE [trastuzumab-vcMMAE]). After conjugation, ADCs were characterized by using UV-vis, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and flow cytometry. The antitumor activity of the ADC was evaluated in breast cancer cells in vitro. In addition, ADCs were further characterized using purification by the protein A chromatography, followed by assessment using apoptosis and MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. Hydrophobic interaction chromatography was used to determine drug-to-antibody ratio species of ADCs produced. Our finding showed that approximately 5.12 drug molecules were conjugated to each mAb. H2L2, H2L, HL, H2, H, and L forms of ADCs were detected in nonreducing SDS-PAGE. The binding of trastuzumab-vcMMAE to HER2-positive cells was comparable with that of the parental mAb. The MTT assay showed that our ADCs induced significant cell death in HER2-positive cells, but not in HER2-negative cells. The ADCs produced was a mixture of species, unconjugated trastuzumab (14.147%), as well as trastuzumab conjugated with two (44.868%), four (16.886%), six (13.238%), and eight (10.861%) molecules of MMAE. These results indicated that MMAE-conjugated trastuzumab significantly increases the cytotoxic activity of trastuzumab, demonstrating high affinity, specificity, and antitumor activity in vitro. Trastuzumab-vcMMAE is an effective and selective agent for the treatment of HER2-positive breast tumors.

Design, synthesis and biological evaluation of peptide-NSAID conjugates for targeted cancer therapy.

Linear arginine-glycine-aspartic acid (RGD) and asparagine-glycine-arginine (NGR) peptide-nonsteroidal anti-inflammatory drug conjugates were synthesized to evaluate their anticancer effect. Two well-known targeting peptide sequences, RGD and NGR, were conjugated with naproxen and ibuprofen. It is expected that the RGD peptide selectively binds to αv -integrin receptors, which are highly expressed in cancer cells, and that the NGR peptide selectively targets aminopeptidase N (APN/CD13, EC 3.4.11.2), which is overexpressed in blood vessels of tumors. To investigate the impact of possible steric hindrance due to the attachment of the drug to the peptide, a linear six-carbon linker (hexanoic acid) was also used as a spacer. Cytotoxic effects of the synthesized compounds were evaluated against several cancer cell lines, including MCF-7, A2780 (αv ß3 positive), OVCAR3 (high αv ß3 ), HT-1-80, and SKOV-3 cells (CD13 positive). The NGR conjugate forms of both ibuprofen and naproxen showed better activity against the SKOV-3 tumor cell line. The improved binding of these conjugates to their receptors was confirmed by docking studies.

Optimization of a dry powder inhaler of ciprofloxacin-loaded polymeric nanomicelles by spray drying process.

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D0.5 of 1.7 µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections.

Effect of Palmitic Acid Conjugation on Physicochemical Properties of Peptide KTTKS: A Preformulation Study.

Lys-Thr-Thr-Lys-Ser (KTTKS) minimally crosses the skin because of hydrophilicity; therefore, its palmitoyl derivative, palmitoyl-KTTKS (Pal-KTTKS), is used in cosmetic products. In spite of this, there is insuffi cient information on its physicochemical properties and the effects of palmitoylation on such properties. The aim of this study was to investigate these properties. Such information would help appropriate formulation development. KTTKS and Pal-KTTKS were synthesized and characterized for ultra violet (UV) absorption, structure [X-ray diffraction (XRD)], morphology (electron microscopy), birefringence (polarized light microscopy), partitioning,solubility, thermal behavior (melting, thermogravimetric analysis, and differential scanning calorimetry), surface activity, critical micelle concentration (CMC, by tensiometry), and stability. KTTKS and Pal-KTTKS decomposed at about 154 and 150°C, respectively, and did not show a melting point before decomposition. The maximum UV absorbance of peptides was less than 200 nm. Both peptides showed birefringence, irregular flake morphologies, and hygroscopicity. KTTKS was freely soluble in water at room temperature (logP = -1.6 ± 0.15), indicating its hydrophilic nature. logP of Pal-KTTKS was calculated to be about 3.7, indicating a lipophilic compound. Pal-KTTKS showed surface activity with a CMC value of 0.024 ± 0.004 mM (19.25 ± 2.9 mg/L),whereas KTTKS did not show such surface activity. Palmitoylation demonstrated sharp peaks in the XRD pattern of KTTKS. KTTKS and Pal-KTTKS differ mainly in terms of chemical properties and show some similarity in physical properties. These results can be used for formulation developments.

Thiosemicarbazone and thiazolylhydrazones of 1-indanone: As a new class of nonacidic anti-inflammatory and antiplatelet aggregation agents.

This research based on the anti-inflammatory and antiplatelet aggregation properties of some new thiazolyl hydrazone derivatives of 1-indanone. In this regard a thiosemicabazone and twelve thiazolyl derivatives of 1-indanone have been synthesized. Out of these synthetic compounds seven derivatives 1-3, 6, 11-13 exhibited varying degree of anti-inflammatory action with IC50 esteems going from 5.1±1.3 - 78.8±4.6µM/mL. Compound 1 (IC50 =5.1±1.9µM) displayed potent result than standard ibuprofen (IC50 = 11.2±1.9 µM). In antiplatelet aggregation assay, five compounds 1, 5, 6, 8 and 11 were observed to be dynamic with IC50 esteems observed in the range of 38.34-255.7±4.1µM, wher eas, aspirin (IC50 = 30.3±2.6 µM) was used as standard. However, compound 11 was found to be good active for both anti-inflammatory and antiplatelet aggregation activities (IC50 = 13.9±4.9µg/mL) (IC50 = 38.60±3.1µM), respectively.

Suppression of migratory and metastatic pathways via blocking VEGFR1 and VEGFR2.

BACKGROUND: Vascular endothelial growth factor (VEGF) A and B are endothelial cell mitogens whose ligation to VEGFR1/VEGFR2 drives tumor angiogenesis and metastasis, and epithelial-mesenchymal transition (EMT). Blockade of these signaling axes could be obtained by disturbing the interactions between VEGFA and/or VEGFB with VEGFR1 and/or VEGFR2. METHODS: A 14-mer peptide (VGB) that recognizes both VEGFR1 and VEGFR2 were investigated for its inhibitory effects on the VEGF-induced proliferation and migration using MTT and scratch assay, respectively. Downstream signaling pathways were also assessed by quantitative estimation of gene and protein expression using real-time PCR and immunohistochemistry (IHC). RESULTS: We investigated the inhibitory effects of VGB on downstream mediators of metastasis, including epithelial-cadherin (E-cadherin), matrix metalloprotease-9 (MMP-9), cancer myelocytomatosis (c-Myc), and nuclear factor-κß (NF-κß), and migration, comprising focal adhesion kinase (FAK) and its substrate Paxilin. VGB inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs), 4T1 and U87 cells in a time- and dose-dependent manner and migration of HUVECs. Based on IHC analyses, treatment of 4T1 mammary carcinoma tumor with VGB led to the suppression of p-AKT, p-ERK1/2, MMP-9, NF-κß, and activation of E-cadherin compared with PBS-treated controls. Moreover, quantitative real-time PCR analyses of VGB-treated tumors revealed the reduced expression level of FAK, Paxilin, NF-κß, MMP-9, c-Myc, and increased expression level of E-cadherin compared to PBS-treated controls. CONCLUSIONS: Our results demonstrated that simultaneous blockade of VEGFR1/VEGFR2 is an effective strategy to fight solid tumors by targeting a wider range of mediators involved in tumor angiogenesis, growth, and metastasis.

Antibacterial activity of some Lamiaceae species against Staphylococcus aureus in yoghurt-based drink (Doogh).

Doogh is a dairy drinkable fermented product, whose shelf-life and quality is mostly affected by bacteria such as Staphylococcus spp.. This study investigated the antibacterial activity of essential oils (EOs) from Thymus vulgaris L., Mentha piperita L. and Ziziphora tenuior L., alone or in combination, against Staphylococcus aureus in industrial doogh. A three-level and three-variable face centered central composite design experiment was used. Results showed that EOs significantly inhibited S. aureus growth after 1 and 7 days of storage. According to the model, the maximum inhibition was obtained in the presence of 0.2% of EO, independently of the type, and no synergistic or additive effects were observed. Slightly lower S. aureus survivals were observed at the maximum concentration of Z. tenuior EO. In spite of the antimicrobial activity of these EOs, further research is needed to assess their performance in food matrix and, in particular, in dairy product.

Thymol, thyme, and other plant sources: Health and potential uses.

Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10-64%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, anti-inflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator. In the present review, these bioactivities have been covered because some of them can contribute to explain the ethnopharmacology of thymol and its main source, T. vulgaris. Other important aspects about thymol are discussed: its toxicity and bioavailability, metabolism, and distribution in animals and humans.

Phytotherapeutics in cancer invasion and metastasis.

Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities.

Preparation of an optimized ciprofloxacin-loaded chitosan nanomicelle with enhanced antibacterial activity.

OBJECTIVE: The objective of this study was to evaluate the effect of lipid structure on physicochemical properties of chitosan-fatty acid nanomicelles and prepare an optimum ciprofloxacin-loaded formulation from these conjugates which could enhance the antibacterial effects of drug against some important pathogens like P. aeruginosa. SIGNIFICANCE: Nowadays, resistance in infectious diseases is a growing worldwide concern. Nanocarriers can increase the therapeutic index and consequently reduce the antibiotic resistance. By site-specific delivery of drug, the adverse effects of broad-spectrum antibiotics such as ciprofloxacin would be reduced. METHODS: Fatty acid grafted chitosan conjugates were synthetized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The effects of fatty acid type (stearic acid, palmitic acid, and linoleic acid) on physicochemical properties of conjugates were investigated. Ciprofloxacin was encapsulated in nanomicelles by thin film hydration method. Also, the preparation process was optimized with a central composite design. The antibacterial effect of optimum formulation against P. aeruginosa, K. pneumoniae, and S. pneumoniae species was determined. RESULTS: All conjugates were synthetized with high yield values and the substitution degrees ranged between 2.13 and 35.46%. Ciprofloxacin was successfully encapsulated in nanomicelles. The optimum formulation showed high drug loading (≈ 19%), with particle size of about 260 nm and a sustained release profile of ciprofloxacin. The minimum inhibitory concentrations of ciprofloxacin in optimum formulation against P. aeruginosa and K. pneumoniae species were 4 and 2 times lower in comparison with the free drug, respectively. CONCLUSIONS: The antibacterial effect of ciprofloxacin was improved by encapsulation of drug in chitosan nanomicelles.

Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

Short Communication - Synthesis of drug metal complexes and their influence on human platelet aggregation.

During the past few decades the emergence of inorganic medicinal chemistry has been developed novel therapeutic agents. Researcher's perseverance in this branch of chemistry has led them to explore further valuable chemical spaces by synthesizing metal complexes already known pharmacological agents for their potential use. However, it is in its early stage, this methodology has demonstrated metal complexes with better bioactivities than the parent ligand molecules. In this study, transition metal complexes of pyrazinamide (PZ), isoniazid (INH), fluconazole (FCZ), metformin (dimethylbiguanide, DMBG) and losartan potassium (LS-K) were selected to evaluate for their possible anti-platelets aggregation in the light of reports on divalent and trivalent cations like calcium, copper, manganese, magnesium, and cadmium may influence the process of thrombocytic activity and aggregation. The required evaluation was carried out on human plasma through an APACT 4004 platelet aggregation analyzer. Arachidonic acid (ADP) was used to gauge any alteration in platelet shape and aggregation process. The parent drugs showed some anti-platelets aggregation, however, their metal complexes demonstrated better efficacy.