Formulation, optimization and characterization of raloxifene hydrochloride loaded PLGA nanoparticles by using Taguchi design for breast cancer application.

Multidrug resistance in breast cancer and the associated side-effects of anticancer therapies are significant hurdles in chemotherapy-based treatment. Biodegradable polymeric nano-based targeted drug delivery technologies showed tremendous advantages in targeted local delivery with limited off-targeted side effects. Therefore, there is a persistent need to develop targeted nanomedicine systems for treatment of breast cancer. The current research attempted to develop poly (lactic-co-glycolic acid) nanoparticles loaded with raloxifene by modified emulsification solvent diffusion evaporation method to improve oral bioavailability by using Taguchi design. It was observed that the optimized formulation (1:4 drug to polymer ratio) poly (lactic-co-glycolic acid) showed a mean particle size and Polydispersity index of 218 ± 23.7 nm and 0.231 ± 0.04, respectively. The entrapment efficiency was found to be 82.30% ± 1.02%. In vitro drug delivery was found to be 92.5% ± 1.48% in 40 h. The nanoparticles were to remain stable at 2°C-8°C even after 30 days. Differential scanning calorimetry and Fourier transform infrared spectroscopy characterization techniques showed that there was no interaction between the drug and excipient. Stability studies indicate that polymeric nanoparticles were stable at 2°C-8°C after 6 months. Raloxifene nanoparticles may be the most potent targeting moieties to treat highly invasive and metastatic MCF-7 breast cancer cells.

Food and drug industry applications of microalgae Spirulina platensis: A review.

Spirulina platensis is a photosynthetic, blue-green, spiral- or bulb-shaped microalgae. Due to the presence of minerals, vitamins, pigments (carotenes, phycocyanin and chlorophyll) proteins (55%-70%), carbohydrates (15%-25%), and essential fatty acids (5%-8%), it has been used as a nutritional supplement for decades. NASA successfully employed it as a nutritional supplement for astronauts on space missions then its popularity was increased. The chemical composition of Spirulina, which is rich in vitamins, minerals, phenolics, vital fatty acids, amino acids, and pigments, can be beneficial to human health when incorporated into meals. The pharmacological effects include antibacterial, anticancer, metalloprotective, immune-stimulating, and antioxidant. It modulates immunological activities and possesses anti-inflammatory qualities by preventing mast cells from releasing histamine. Due to its high quantity of protein, carbohydrate, lipid, vital amino and fatty acids, dietary minerals and vitamins, Spirulina exerts the abovementioned benefits. In this review, up-to-date and possible biological aspects, patents applied on Spirulina and heights of confirmation are addressed, and the extent of current and future exploration is also explored.

Design expert assisted formulation, characterization and optimization of microemulsion based solid lipid nanoparticles of repaglinide.

Repaglinide, a member of the meglitinide class of drugs, is a new anti-diabetic agent that is utilized as an oral hypoglycemic agent. Using glyceryl monostearate, cetyl palmitate, and tristearin as lipids and poloxamer 188 as a surfactant, repaglinide-loaded solid lipid nanoparticles were created. Solid lipid nanoparticles were prepared utilizing an o/w microemulsion technique, which included the lipids glyceryl monostearate and tristearin, as well as waxes such as cetyl palmitate and the surfactant poloxamer 188. The mean particle size of the solid lipid nanoparticles formed was around 339 nm, with an entrapment efficiency of 82.20%. In-vitro release studies continued to be conducted using the dialysis bag diffusion technique. Within 12 h, the cumulative drug release was 88.4%. The results indicate that repaglinide was released more slowly from solid lipid nanoparticles made from tristearin and glyceryl monostearate in an equal ratio. Tristearin found the controlled release and extreme entrapment from other lipid carriers like glyceryl monostearate and cetyl palmitate. Differential scanning calorimetry demonstrates that repaglinide is entangled in amorphous or molecular state within solid lipid nanoparticles. SEM microscopy revealed that the produced repaglinide solid lipid nanoparticles had a spherical shape. After one month of storage at 2-8 °C, short-term stability testing revealed no significant alteration.

Formulation and evaluation of thermosensitive flurbiprofen in situ nano gel for the ocular delivery.

The contemporary research implicates the formulation and evaluation of a thermosensitive in situ nano gelling method to improve solubility and ocular residence time of flurbiprofen. This study was carried out in two phases. In the first phase, an insolubility drug has been formulated in the form of a nanoparticulate system and evaluated for its characteristics. The nanoparticles obtained demonstrated an average size array of 150 to 250 nm in diameter, up to 79.35% encapsulation efficiency, and up to 93.42% drug release throughout 2 h. In the second phase, nanoparticulate systems were dispersed in aqueous solutions of Pluronic F 127 (14%) and various concentrations of Carbopol 934 in combination to form an in situ nano gel. The prepared in situ gel was investigated for its physicochemical properties like pH, flowability, sol-gel transition temperature, gelling capacity, and rheological properties. Carbopol 934 did not significantly affect sol-gel transition temperature in optimized concentration (<0.3%) but altered gelling capacity, pH, and transparency of the formulations. In vivo resident time and eye irritation test was evaluated in the rabbit eye. In optimized in situ gelling formulation (NIGF3), approximately 95% of in vitro drug release was observed after 6 h. NIGF3 increased precorneal residence time and high concentration in aqueous humor when paralleled to flurbiprofen eye drops. Greater concentration of drug in aqueous humor was due to its improved saturation solubility of the drug, and amplified residence time was attributed to the formation of gel matrix-embedded nanoparticles. This demonstrated that in situ nano gels (NIGF3) comprehending aqueous solutions of 0.3% w/v concentrations of Carbopol 934 with Pluronic F 127 may ominously persist the residence time and mend bioavailability of a water-insoluble drug.

Colorimetric and fluorescence sensing of Zn2+ ion and its bio-imaging applications based on macrocyclic "tet a" derivative.

We report on the synthesis and characterization of trans N, N'-di-substituted macrocyclic "tet a" probe (L) for metal ion sensing. Both the colorimetric and fluorescent titration studies are performed with different metal ions. The results have suggested that the probe L is very selective and sensitive towards Zn2+ ions with significant changes in color. The pendant armed macrocyclic "tet a" probe has exhibited 1.28× 105 M-1 binding constant and virtuous selectivity for Zn2+ ion than other common metal ions. The detection limit of the probe towards Zn2+ ion is 0.027 nM. The selective sensing of Zn2+ ion is efficiently reversible with EDTA, which is demonstrated for five cycles without losing sensitivity. The time-resolved single-photon counting (TCSPC) studies have determined the average lifetime value for the probe L and L+ Zn2+ ion of 1.29 and 2.96 ns, respectively. The theoretical DFT studies have well supported the experimental outcomes. The practical application of the probe in visualizing intracellular Zn2+ ion distribution in live Artemia salina has proved the low cytotoxicity and cell membrane permeability of probe, which makes it capable of sensing Zn2+ ion in HeLa cells. Thus, the probe L can act as a selective recognition of Zn2+ ion in living cell applications.

Phenothiazine-rhodamine-based colorimetric and fluorogenic 'turn-on' sensor for Zn2+ and bioimaging studies in live cells.

A phenothiazine-rhodamine (PTRH) fluorescent dyad was synthesized and its ability to selectively sense Zn2+ ions in solution and in in vitro cell lines was tested using various techniques. When compared with other competing metal ions, the PTRH probe showed the high selectivity for Zn2+ ions that was supported by electronic and emission spectral analyses. The emission band at 528 nm for the PTRH probe indicated the ring closed form of PTRH, as for Zn2+ ion binding to PTRH, the λem get shift to 608 nm was accompanied by a pale yellow to pink colour (under visible light) and green to pinkish red fluorescence emission (under UV light) due to ring opening of the spirolactam moiety in the PTRH ligand. Spectral overlap of the donor emission band and the absorption band of the ring opened form of the acceptor moiety contributed towards the fluorescence resonance energy transfer ON mechanism for Zn2+ ion detection. The PTRH sensor had the lowest detection limit for Zn2+ , found to be 2.89 × 10-8  M. The sensor also demonstrated good sensing application with minimum toxicity for in vitro analyses using HeLa cells.

Effect of substitution on the excited state photophysical and spectral properties of boron difluoride curcumin complex dye and their derivatives: A time dependent-DFT study.

The optical, charge transport and electronic properties of boron difluoride curcumin (BFC) complex have been explored using the DFT (Density Functional Theory) method and B3LYP functional with the combination of 6-31 + G(d,p) as a basis set. The influence of substitution with various electron releasing and withdrawing groups on the above properties is analyzed and discussed in this work. The results reveal that the BFC complex on additional electron releasing substitution experiences redshifts in the optical transitions, and this is correlated with the dipole moment, NBO charges, HOMO-LUMO energy gap. Further, the absorption (λabs) and emission (λems) spectra of substituted and unsubstituted BFCs are calculated using Time-Dependent Density Functional Theory (TD-DFT). The results show that the electron releasing groups strongly influence the absorption and emission spectra of BFC. Electron releasing groups in BFC derivatives generate the wavelength shift (Bathochromic), but the electron-withdrawing groups in BFC don't affect the λabs and λems when compare to its original (parent) compound. The output of the research work strongly recommends that the amino, phenyl and N, N'-dimethylamino derivatives are potential candidates to act as fluorescent materials due to enhance the emission behavior of BFC and also can be used as an electron/charge transport material for organic light-emitting diodes (OLEDs).

Execution of julolidine based derivative as bifunctional chemosensor for Zn2+ and Cu2+ ions: Applications in bio-imaging and molecular logic gate.

A simple julolidine based chemosensor (JT) was designed and synthesized by single condensation step. JT displayed excellent selectivity and sensitivity with on-off responses towards Zn2+ and Cu2+ over other biologically relevant metal ions in aqueous media. Upon addition of Zn2+ ions, JT exhibited a significant blue shift in emission followed by turn-on enhancement while with Cu2+, the fluorescence intensity of JT was completely vanished. The 1:1 binding affinity between JT and Zn2+/Cu2+ was proposed by Job's plot analysis. The detection limit for Zn2+ and Cu2+ ions reached at 3.5 × 10-8 M and 1.46 × 10-6 M, respectively. The sensing mechanism of JT with Zn2+/Cu2+ was supported by DFT calculations. Based on photophysical studies and its reversibility environment with EDTA, molecular logic gates were fabricated. Furthermore, JT was successfully established to detect intracellular Zn2+ ions in live cells by turn-on response.

A Fluorescent Turn-On Carbazole-Rhodanine Based Sensor for Detection of Ag+ Ions and Application in Ag+ Ions Imaging in Cancer Cells.

Carbazole - Rhodanine conjugate is an effective fluorescent host for silver ions through fluorometric transformation from green to red color with a hyperchromic emission. An intramolecular charge transfer process derived from carbazole towards rhodanine favors interaction of thiocarbonyl S and carboxylic acid O of the rhodanine moiety towards Ag+ ion. Carbazole - rhodanine dyad accomplishes the lowest detection limit of 12.8 × 10-9 M and high quantum efficiency. A fluorescence reversibility of the probe with I- ion surges reutilization of sensor molecule as an Ag+ ion probe with minimal loss in the fluorescent efficiency. This fluorescent ligand is a biocompatible probe and is also a proficient candidate for fluorescent imaging of Ag+ ion in live cells.

Carbazole-azine based fluorescence 'off-on' sensor for selective detection of Cu2+ and its live cell imaging.

A new carbazole-azine based fluorescent sensor was synthesized and characterized. The selectivity of the sensor for Cu2+ over other counter ions in a dimethyl sulfoxide/H2 O mixture was shown through enhancement in fluorescence - an off to on transformation. The specificity of the probe towards Cu2+ was evident in ultraviolet/visible, fluorescence, Fourier transform infrared and mass studies. Application of the probe in the cell imaging and cytotoxicity of living cells is illustrated.