Formulation and Optimization of Self Emulsifying Drug Delivery System For Effective Anthelmintic Therapy

The present study aims to develop and optimize a self-emulsifying drug delivery system for paediatric patients to improve the oral bioavailability of the anthelmintic drug, Praziquantel (PZQ) and to perform it’s in-vitro dissolution study. The solubility of PZQ was estimated in various vehicles to select proper component combination. Capmul MCM (oil), Cremophore RH40 (surfactant) and PEG400 (co-surfactant) were employed to construct pseudo-ternary phase diagrams. Eight formulations composed of Capmul MCM, at Smix ratios (1:1, 2:1 & 3:1) were selected. The optimized formulation F7 has a mean globule size 14.73 nm with a negative zeta potential -44.43 mV. The results indicated that PZQ loaded SEDDS, showed enhanced solubilization and nanosizing potential to improve the absorption of the drug.

Response of Rhodococcus cerastii IEGM 1278 to toxic effects of ibuprofen

The article expands our knowledge on the variety of biodegraders of ibuprofen, one of the most frequently detected non-steroidal anti-inflammatory drugs in the environment. We studied the dynamics of ibuprofen decomposition and its relationship with the physiological status of bacteria and with additional carbon and energy sources. The involvement of cytoplasmic enzymes in ibuprofen biodegradation was confirmed. Within the tested actinobacteria, Rhodococcus cerastii IEGM 1278 was capable of complete oxidation of 100 μg/L and 100 mg/L of ibuprofen in 30 h and 144 h, respectively, in the presence of an alternative carbon source (n-hexadecane). Besides, the presence of ibuprofen induced a transition of rhodococci from single- to multicellular lifeforms, a shift to more negative zeta potential values, and a decrease in the membrane permeability. The initial steps of ibuprofen biotransformation by R. cerastii IEGM 1278 involved the formation of hydroxylated and decarboxylated derivatives with higher phytotoxicity than the parent compound (ibuprofen). The data obtained indicate potential threats of this pharmaceutical pollutant and its metabolites to biota and natural ecosystems.

Formulation design and evaluation of aceclofenac nanogel for topical application

Aim: The current study aimed to explore the feasibility of the nanoemulgel for the topical delivery of aceclofenac. Materials & methods: Solubility of drugs in the formulation systems was determined and aceclofenac nanoemulsion (NE) was prepared by high-pressure homogenization technique. Carbopol 940 was added as a gelling agent. Results & conclusion: The composition of optimized NE consist of labrafil along with triacetin as oil, tween 80 and cremophor EL in combination as a surfactant and transcutol HP along with PEG 400 and ethanol as cosurfactant. The droplet size of the NE was 141.1 ± 3.65 nm, with low polydispersity index and negative zeta potential. The aceclofenac–nanoemulgel was developed using carbopol 940 and exhibited excellent permeation in comparison to the marketed sample.

Microparticle Deposition on Human Serum Albumin Layers: Unraveling Anomalous Adsorption Mechanism

Human serum albumin (HSA) layers are adsorbed on mica under controlled diffusion transport at pH 3.5 and various ionic strengths. The surface concentration of HSA is directly determined by AFM imaging of single molecules. It is shown that the adsorption kinetics derived in this way is quantitatively described using the random sequential (RSA) adsorption model. The electrokinetic characteristics of the HSA layers at various pHs comprising their zeta potential are acquired in situ while using the streaming potential method. It is shown that at pH 3.5 the zeta potential of mica becomes positive for HSA concentrations above 3000 μm−2. At larger pHs, HSA layers exhibit negative zeta potential for the entire range of coverage. Thorough characteristics of these monolayers at various pHs were performed applying the colloid deposition method involving negatively charged polystyrene microparticles. The kinetics of their deposition and their maximum coverage are determined as a function of the HSA layer surface concentration, pH, and ionic strength. An anomalous deposition of microparticles on substrates also exhibiting a negative zeta potential is observed, which contradicts the Derjaguin, Landau, Vervey, Overbeek (DLVO) theory. This effect is interpreted in terms of heterogeneous charge distribution that results from molecule concentration fluctuations. It is also shown that the maximum concentration of microparticles abruptly decreases with the electric double-layer thickness that is regulated by changing ionic strength, which indicates that their deposition is governed by electrostatic interactions. One can argue that the results obtained in this work can be exploited as useful reference data for the analysis of deposition phenomena of bioparticles on protein layers.

The Effects of Ethanol Concentration and of Ionic Strength on the Zeta Potential of Titania in the Presence of Sodium Octadecyl Sulfate

Sodium octadecyl sulfate (C18H37SO4Na) induces a negative zeta potential of metal oxides at very low surfactant concentrations as compared with shorter-chained sodium alkyl sulfates. The problem of low solubility of sodium octadecyl sulfate in water was solved by the addition of the surfactant to dispersions as ethanolic stock solution, but then the presence of ethanol in dispersions was inevitable. We demonstrate that the concentration of ethanol (up to 5% by mass) in a dispersion containing titania (TiO2) and sodium octadecyl sulfate has an insignificant effect on the zeta potential of particles. We further demonstrate that the shifts in the IEP of titania induced by the presence of sodium octadecyl sulfate are independent of the NaCl concentration. The results obtained in this study can be generalized for 1-1 salts other than NaCl, for metal oxides other than titania, for organic co-solvents other than ethanol, and for sparingly soluble ionic surfactants other than sodium octadecyl sulfate.

Tantalum-containing mesoporous bioactive glass powder for hemostasis

This study evaluates the hemostatic properties of tantalum-containing mesoporous bioactive glasses (Ta-MBGs) through a suite of in-vitro methods: hemolysis percentage, zeta potential, blood coagulation assays (Activated Partial Thromboplastin Time – APTT and Prothrombin Time - PT) and cytotoxicity tests. Five compositions of Ta-MBG, with x mol% Ta2O5 added to the glass series (80- x)SiO2-15CaO-5P2O5- xTa2O5 where x=0 (0Ta), x=0.5 (0.5Ta), x=1 (1Ta), x=5 (5Ta), and x=10 (10Ta) mol%, were synthesised. The hemostatic potential of all the Ta-MBGs was confirmed by their negative zeta potential (–23 to –31 mV), which enhances the intrinsic pathway of blood coagulation. The hemolysis percentages of all Ta-MBGs except 10Ta showed statistically significant reductions compared to the same experiments carried out both in the absence of a sample (‘no treatment’ group) and in the presence of 10Ta. These observations validate the consideration of Ta-MBGs as hemostatic agents as they do not cause significant lysis of red blood cells. Cytotoxicity analysis revealed that Ta-MBGs had no effect on bovine fibroblast viability. Furthermore, a reduction in both APTT (a test to evaluate the intrinsic pathway of coagulation) and PT (a test to evaluate the extrinsic pathway) signified enhancement of hemostasis: 5Ta caused a significant reduction in APTT compared to ‘no treatment’, 1Ta and 10Ta and a significant reduction in PT compared to 0Ta. Therefore, we conclude that 5mol% of Ta optimised the hemostatic properties of these mesoporous bioactive glasses.

Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients

UVB phototherapy is treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. Therefore, we carried out lipidomic analysis on the keratinocytes of healthy individuals and patients with psoriasis irradiated with UVB and treated with cannabidiol (CBD), phytocannabinoid with antioxidant and anti-inflammatory properties. Our results showed that, in psoriatic keratinocytes phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), and ether-linked phosphoethanolamine (PEo), were downregulated, while SM (d41:2) was upregulated. These changes were accompanied by an increase in negative zeta potential, which indicates translocation of PS to the outer layer of the membrane. CBD treatment of psoriatic keratinocytes led to downregulation of PC, PS, and upregulation of certain PEo and an SM species, SM (d42:2), and the zeta potential. However, UVB irradiation of psoriatic keratinocytes resulted in upregulation of PC, PC plasmalogens (PCp), PEo, and a decrease in the negative zeta potential. The exposure of UVB-irradiated cells to CBD led to a decrease in the level of SM (d42:2). Our results suggest that CBD induces pro-apoptotic mechanisms in psoriatic keratinocytes while simultaneously improving the antioxidant properties and preventing the loss of transepidermal water of keratinocytes of patients irradiated with UVB. Thus, CBD has potential therapeutic value in the treatment of psoriasis.

pH-Responsive Polyketone/5,10,15,20-Tetrakis-(Sulfonatophenyl)Porphyrin Supramolecular Submicron Colloidal Structures

In this work, we prepared color-changing colloids by using the electrostatic self-assembly approach. The supramolecular structures are composed of a pH-responsive polymeric surfactant and the water-soluble porphyrin 5,10,15,20-tetrakis-(sulfonatophenyl)porphyrin (TPPS). The pH-responsive surfactant polymer was achieved by the chemical modification of an alternating aliphatic polyketone (PK) via the Paal–Knorr reaction with N-(2-hydroxyethyl)ethylenediamine (HEDA). The resulting polymer/dye supramolecular systems form colloids at the submicron level displaying negative zeta potential at neutral and basic pH, and, at acidic pH, flocculation is observed. Remarkably, the colloids showed a gradual color change from green to pinky-red due to the protonation/deprotonation process of TPPS from pH 2 to pH 12, revealing different aggregation behavior.

Combination of Curcumin and Paclitaxel Liposomes Exhibits Enhanced Cytotoxicity Towards A549/A549-T Cells and Unaltered Pharmacokinetics

Background: Combination chemotherapy of chemo-drugs and natural herbal drugs has been shown to be more advantageous than individual treatment with respect to enhancing cytotoxicity, alleviating toxicity and controlling the development of multidrug resistance (MDR). Purpose: The goal of this study is to construct a combined drug delivery system of curcumin liposomes (CUR-LPs) and paclitaxel liposomes (PTX-LPs) to enhance the anticancer activity and reverse the MDR of PTX. Methods: CUR-LPs and PTX-LPs were prepared by solvent evaporation method with optimal formulation composition. MTT assay was used to assess the effect of the combination of CUR-LPs and PTX-LPs treatments on the proliferation of A549/A549-T cells. In addition, the pharmacokinetic behaviors of the combination treatments were evaluated by HPLC. Results : The mixed liposomes were found to have negative zeta-potential (–17.91 ± 1.21 mV) and relatively uniform particle size (105.88 ± 3.19 nm) with a low polydispersity index (0.21 ± 0.016). IC50 of PTX for combination of CUR-LPs and PTX-LPs decreased in the range of 1.47–2.9 times and 1.59–2.5 times compared to the free-drug counterparts in A549 and A549-T cells, respectively. Superior cytotoxicity and higher synergy (CI< 0.4) were observed for the combination treatment with ratio of 40:1 (CUR-LPs:PTX-LPs) compared with the free-drug counterparts in both cell lines tested. Following intravenous administration in rats, liposomes presented higher bioavailability (CUR-LPs: 9.02 fold; PTX-LPs: 7.32 fold) compared to free drugs. Co-administration did not alter the respective pharmacokinetic behaviors. Conclusion: Overall, the present study presents a promising strategy for the development of compound formulations of CUR and PTX.