Propagation of Gaussian Schell-model beams in modulated graded-index media.

The evolution of partially coherent beams in longitudinally modulated graded-index media is studied. The special cases of Gaussian Schell-model beams and parametric modulation, when the modulation period is half the fiber self-imaging period, are examined in detail. We show that the widths of the intensity and coherence of Gaussian Schell-model beams undergo amplification in parametrically modulated parabolic graded-index media. The process is an analog of quantum mechanical parametric amplification and generation of squeezed states. Our work may find application in spatial and temporal imaging of partially coherent beams in fiber-based imaging systems.

Soliton supermode transitions and total red shift suppression in multi-core fibers.

Soliton propagation in seven-core fibers is studied numerically with the frequency dependence of linear coupling taken into account. It is shown that under certain conditions, solitons can undergo spontaneous supermode transitions upon abrupt red shift, analogous to the recently discovered phenomenon of soliton self-mode conversion in step-index multi-mode fibers. When the core separation is increased, the dynamics change drastically, leading to total suppression of soliton self-frequency shift and the emergence of spatially oscillating solitonic structures with resemblance to solitons in graded-index multi-mode fibers. The observed phenomena are general multi-core effects and not specific to seven-core fibers.

Folate Conjugated Double Liposomes Bearing Prednisolone and Methotrexate for Targeting Rheumatoid Arthritis.

PURPOSE: This investigation was aimed to explore the targeting potential of folate conjugated double liposomes (fDLs) bearing combination of synergistic drugs (Prednisolone and Methotrexate) for effective management of the rheumatoid arthritis (RA). METHODS: To overcome the drawbacks of monotherapy, a combination of prednisolone (PRD) (an anti-inflammatory agent) and methotrexate (MTX) (a disease modifying anti-rheumatoid agent, DMARDs) was chosen for dual targeting approach. fDLs were prepared in two steps i.e. development of inner liposomes (ILs) using thin film casting method followed by encapsulation of ILs within folate conjugated outer liposomes (double liposomes; fDLs). Developed liposomes were characterized for various physicochemical parameters and in vivo performance. RESULTS: fDLs were prepared using FA-PEG-4000-NH-DSPE conjugate. These double liposomes were having 429.3 ± 3.6 nm in size with 0.109 PDI, 8.01 ± 0.3 mV zeta potential (ζ) and 66.7 ± 3.9% and 45.3 ± 1.7% entrapments of PRD and MTX, respectively. After 24 h, the concentrations of PRD in blood were observed to be 8.66 ± 3.11 (ILs) and 15.13 ± 0.81% (DLs) while concentration of MTX were found to be 10.89 ± 0.69 and 2.34 ± 3.15% when given as ILs and fDLs, respectively. The concentration of both drugs in inflamed joint was observed to be higher than that in the non-inflamed joints. CONCLUSIONS: The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.

Fate of a Soliton in a High Order Spatial Mode of a Multimode Fiber.

We show numerically that under certain conditions noise-induced soliton self-mode conversion dominates over soliton self-frequency shift for a soliton in a high order spatial mode of a multimode optical fiber. The input soliton has to be group index matched to a lower order mode for a frequency separation for which the Raman gain is non-negligible, and this condition determines the wavelength of the pulse growing from noise. The phenomenon has no known analogs in single-mode or graded-index fibers. The results demonstrate that it is possible for a noise-induced physical process to dominate over a seeded one even for noise levels at the fundamental limit.

What is the Temporal Analog of Reflection and Refraction of Optical Beams?

It is shown numerically and analytically that when an optical pulse approaches a moving temporal boundary across which the refractive index changes, it undergoes a temporal equivalent of reflection and refraction of optical beams at a spatial boundary. The main difference is that the role of angles is played by changes in the frequency. The frequency dependence of the dispersion of the material in which the pulse is propagating plays a fundamental role in determining the frequency shifts experienced by the reflected and refracted pulses. Our analytic expressions for these frequency shifts allow us to find the condition under which an analog of total internal reflection may occur at the temporal boundary.

Plastic fiber design for THz generation through wavelength translation.

We report on an all-fiber terahertz (THz) radiation source by exploiting nonlinear parametric process in a theoretically designed microstructured-core double-clad plastic fiber (MC-DCPF). The required phase-matching condition is satisfied through suitable tailoring of the fiber dispersion and nonlinear properties at the pump wavelength of a high-power CO2 laser, with a CO laser of much lower power acting as a seed concomitantly. Our simulated results reveal that a THz radiation source at the frequency of ∼3 THz could be realized with a 3-dB phase-matching band width of 2.13 GHz in a 65-m-long optimized MC-DCPF. Maximum power conversion efficiency >1% is realizable even after including the material loss.

Dispersion engineered Ge11.5As24 Se64.5 nanowire for supercontinuum generation: a parametric study.

A promising design of Ge11.5As24 Se64.5 nanowires for supercontinuum generation is proposed through numerical simulations. It can be used for generating a supercontinuum with 1300-nm bandwidth. The dispersion parameters upto eighth-order are obtained by calculating the effective mode index with the finite-element method. We have investigated dispersion curves for a number of nanowire geometries. Through dispersion engineering and by varying dimensions of the nanowires we have identified a promising structure that shows possibility of realizing a wideband supercontinuum. We have found significant variations in its bandwidth with the inclusion of higher-order dispersion coefficients and indicated the possibility of obtaining spurious results if the adequate number of dispersion coefficients is not considered. To confirm the accuracy of dispersion coefficients obtained through numerical computations, we have shown that a data-fitting procedure based on the Taylor series expansion provides good agreement with the actual group velocity dispersion curve obtained by using a full-vectorial finite-element mode-solver.

Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.

The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

Polymeric nanomedicines as a promising vehicle for solid tumor therapy and targeting.

Inspite of demanding research that has been undertaken for cancer treatment, cancer is a major cause of mortality. Available conventional treatment options of solid tumor are associated with serious side effects. Nanomedicines mediated fascinating approach may be effectively utilized for efficient tumor targeting by avoiding all the problems associated with conventional chemotherapy. Polymeric nanomedicines such as polymer micelles, polymeric nanoparticles, polymersomes and polymer conjugates currently developed for solid tumor treatment have proved to be efficacious cancer therapeutics. These polymeric nanostructures are able to reach tumor tissue or angiogenic endothelial cells either passively or actively. To date, more advancement in the tumor targeting field includes stimuli sensitive polymeric nanocarriers that pass through the intracellular delivery barriers and release the bioactives in response to the microenvironmental trigger of tumor cell. This review discusses the molecular aspects of solid tumor pathophysiology and its dramatic impact on research for innovative and novel therapeutic approaches linked with tumor-targeting polymeric nanomedicines.

Functionalized carriers for the improved delivery of plasminogen activators.

Various plasminogen activators have been routinely used for the treatment of thrombotic diseases. However, these agents possess various problems e.g. short half life and other bleeding complications. To improve the effectiveness as well as to reduce the side effects of these drugs, various modifications have been made. For example, fibrin specific plasminogen activators have been developed. However, these agents also demonstrated various bleeding complications, clinically. Nowadays, so many carrier systems have been explored to improve the activity of these agents. Novel carriers not only improve the effectiveness of these drugs but also reduce the side effects. In the present review, we discuss novel carrier based strategies to improve the delivery of the plasminogen activators to site of thrombus.

Platelets directed liposomes for the delivery of streptokinase: development and characterization.

The present study was aimed to study the effect of RGD peptide conjugation on the bio-distribution behaviour of long circulatory liposomes in the thrombosed rat model. Further, thrombolysis study was also performed to evaluate the therapeutic activity of the prepared liposomes. Liposomes were prepared by film hydration method and peptide was subsequently conjugated on the preformed liposomes using carbodiimide chemistry. Prepared liposomes were characterized for size and size distribution, entrapment efficiency and in vitro drug release. In vitro targeting ability of the liposomes was determined by platelets binding assay. In vivo studies were performed in the rat model containing human blood clot inoculated in the carotid artery. Results of the study showed that RGD peptide conjugated liposomes significantly accumulated to the site of blood clot and higher thrombolytic activity was observed with peptide modified liposomes as compared to plain streptokinase solution and long circulatory liposomes.

Development and characterization of site specific target sensitive liposomes for the delivery of thrombolytic agents.

In recent times, search for potent and highly selective thrombolytic agents with minimal side effects has become a major area of research. The aim of the present study was to develop and characterize target sensitive (TS) liposomes encapsulating streptokinase, a thrombolytic agent. The developed TS liposomes were composed of dioleylphophatidyl ethanolamine (DOPE) and dipalmityl-c(RGDfK) (10:1mol/mol). Dipalmityl-c(RGDfK) was synthesized using typical carbodiimide chemistry using palmitic acid and c(RGDfK), while lysine was used as a spacer. Liposomes were of 100-120nm size. In vitro drug release study showed that nearly 40% drug of the entrapped drug was released in 12h in the PBS (pH 7.4), however on incubation with activated platelet about 90% of drug was released within 45min. The results suggested target sensitivity of the liposomes. Further, targeting potential was confirmed using fluorescent microscopy and flow cytometry. Clot lysis study revealed that TS liposomes could not only reduce the clot lysis time but also increase the extent of clot lysis as compared to non-liposomal streptokinase solution. In conclusion, the present liposomal formulation will target the thrombolytic agent to the activated platelets in the thrombus and hence will improve the therapeutic efficacy of the drug.

Gelatin nanocarriers as potential vectors for effective management of tuberculosis.

The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticulate delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through transmission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistribution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264+/-11.2 nm with low PDI suggesting the narrow particle size distribution. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis.

Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting.

The objective of the present study was to evaluate the prospective of engineered nanoparticles for selective delivery of an antituberculosis drug, rifabutin, to alveolar tissues. Drug-loaded solid lipid nanoparticles (SLNs) were synthesized and efficiently mannosylated. The formation of uncoated and coated SLNs was characterized by FTIR spectroscopy and SEM studies. A variety of physicochemical parameters such as drug loading, particle size, polydispersity index, zeta potential, and in vitro drug release were determined. The toxicity and targeting potential of the prepared formulation were assessed with alveolar macrophage uptake, hematological studies, and in vivo studies of uncoated and coated SLNs. Ex vivo cellular uptake studies of SLNs formulations in alveolar macrophages depicted almost six times enhanced uptake due to mannose coating. The hematological studies proved mannose-conjugated system to be less immunogenic and suitable for sustained delivery as evaluated against uncoated formulation. Further, the serum level and organ distribution studies demonstrated efficiency of the system for prolonged circulation and spatial delivery of rifabutin to alveolar tissues. Finally, it was concluded that mannose-conjugated SLNs can be exploited for effective and targeted delivery of rifabutin compared to its uncoated formulation and ultimately increasing the therapeutic margin of safety while reducing the side effects.

Nanoparticles as novel carrier for brain delivery: a review.

Blood Brain Barrier (BBB) represents a major hurdle for the delivery of bioactives in the brain. It serves as a major constraint for the entry of hydrophilic drugs and the efflux pumps present on its surface restrain the intracellular accumulation of pharmacological moieties in the brain. Nanoparticles (NPs) in this regard can serve as a potential module for ferrying large doses of drugs across the BBB. These can be coated at surfaces or fabricated with a targeting moiety, so as to gain access in the brain thus, minimizing the toxicity of therapy. Therefore, the NPs can serve as an exclusive dais for spatial and temporal distribution of pharmacological agents across the brain, escalating the probability of disease free survival. The current review explores the various possible mechanisms so that the NPs can gain access in the brain viz a viz adsorption, receptor mediated endocytosis, transcytosis, inhibiting p-glycoprotein efflux pump, membrane permeabilization effect and disrupting the BBB. The article also accounts the prospects of NPs to enhance the transport of therapeutic agents across the brain, providing refined drug delivery.

Preparation and characterization of HA-PEG-PCL intelligent core-corona nanoparticles for delivery of doxorubicin.

The objective of the present study was to synthesize core-corona nanoparticles of doxorubicin (DOX) using hyaluronic acid-polyethyleneglycol-polycaprolactone (HA-PEG-PCL) copolymer for tumor targeting. Targeting efficiency of HA-PEG-PCL nanoparticles was compared with non-HA-containing nanoparticles (methoxy poly ethylene glycol (MPEG)-PCL). The copolymers were chemically synthesized and characterized by IR and NMR spectroscopies. The nanoparticles were characterized for shape and morphology by transmission electron microscopy, particle size, percentage of drug entrapment, and in vitro drug release profile. Differential scanning calorimetry and X-ray diffraction studies were also performed to appraise the crystalline or amorphous nature of DOX inside the polymer matrix. Formulations were prepared using different DOX:polymer ratios (1:1-1:3 w/w) and the optimum formulation with the drug:polymer ratio of 1:1 showed the mean particle size of 95 +/- 5 nm and entrapment efficiency of 95.56% in the case of HA-PEG-PCL nanoparticles, while the values were 115 nm and 95.50%, respectively, in the case of MPEG-PCL nanoparticles. The HA-PEG-PCL nanoparticles could release DOX for up to 17 days, whereas the MPEG-PCL nanoparticles could release it for up to 14 days. The hemolytic toxicity and hematological studies confirmed that both DOX-loaded HA-PEG-PCL and MPEG-PCL nanoparticles were safe and suitable for sustained and targeted drug delivery. The tissue distribution study and tumor growth inhibition were performed after intravenous injection of nanoparticles in Ehrlich ascites tumor (EAT)-bearing mice. The nanoparticles of HA-PEG-PCL copolymer accomplishes efficient delivery of DOX in EAT tumor when compared with the MPEG-PCL nanoparticles by the process of receptor-mediated endocytosis, as well as enhanced permeability and retention effect.

Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin.

Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of beta-cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with beta- cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 microg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 microg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with beta-cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.

In vitro evaluation of porous carrier-based floating granular delivery system of orlistat.

The purpose of the study is to prepare and evaluate an intragastric floating granular delivery system of orlistat using (i) calcium silicate as porous carrier; and (ii) hydroxypropyl methylcellulose K4M, ethyl cellulose, and Carbopol 940 as matrix-forming polymers. The effect of various formulation and process variables on the micro-meritic properties, in vitro floating behavior, percent drug content, and in vitro drug release was studied. The release mechanism of orlistat from these granules was evaluated on the basis of various theoretical equations. The optimized formulation demonstrated favorable in vitro floating and release characteristics. The release pattern of optimized, secondary-coated granules of orlistat in simulated gastrointestinal fluids corresponded best to the Peppas-Korsmeyer model and Higuchi matrix model. The results clearly indicated the controlled and sustained release of orlistat from its gastro-retentive floating granular delivery system.

Development of mesophasic microreservoir-based transdermal drug delivery system of propranolol.

The mesophasic microreservoir comprises lyotrophic liquid crystals. The liquid crystals were prepared of Brij-35, cetosteryl alcohol and propranolol and evaluated for parameters viz. anisotropy, size and size distribution and drug entrapment efficiency. Subsequent to this liquid crystals based transdermal drug delivery system (TDS) was prepared by incorporating liquid crystals in previously prepared matrix based transdermal patch and evaluated for stability studies like temperature, humidity and aging. The system was also studied for tensile strength, moisture content, water vapor transmission, drug content, anisotropy and In vitro drug release studies.

Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate.

Polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM) were prepared by emulsion solvent evaporation method to improve its photostability and effectiveness as sunscreening agent. Process parameters like stirring speed and aqueous polyvinyl alcohol (PVA) concentration were analyzed in order to optimize the formulations. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The PMMA microspheres of EHM were incorporated in water-removable cream base. The in vitro drug release of EHM in pH 7.4 was performed using dialysis membrane. Thin layer chromatography was performed to determine photostability of EHM inside the microspheres. The formulations were evaluated for sun protection factor (SPF) and minimum erythema dose (MED) in albino rats. Cream base formulation containing microspheres prepared using EHM:PMMA in ratio of 1:3 (C(3)) showed slowest drug (EHM) release and those prepared with EHM: PMMA in ratio of 1:1 showed fastest release. The cream base formulations containing EHM loaded microspheres had shown better SPF (more than 16.0) as compared to formulation C(d) that contained 3% free EHM as sunscreen agent and showed SPF 4.66. These studies revealed that the incorporation of EHM loaded PMMA microspheres into cream base had greatly increased the efficacy of sunscreen formulation approximately four times. Further, photostability was also shown to be improved in PMMA microspheres.