Antifungal Carvacrol Loaded Chitosan Nanoparticles

The increased prevalence and incidence of fungal infections, of which Candida albicans represents one of the most life-threatening organisms, is prompting the scientific community to develop novel antifungal molecules. Many essential oils components are attracting attention for their interesting antifungal activities. Given the chemical and physical characteristics of these compounds, the use of appropriate nanodelivery systems is becoming increasingly widespread. In this study, chitosan nanoparticles were prepared using an ionic gelation procedure and loaded with the phenolic monoterpene carvacrol. After a bioassay guided optimization, the best nanoparticle formulation was structurally characterized by means of different spectroscopic (UV, FTIR and DLS) and microscopy techniques (SEM) and described for their functional features (encapsulation efficiency, loading capacity and release kinetics). The antifungal activity of this formulation was assayed with different Candida spp., both in planktonic and biofilm forms. From these studies, it emerged that the carvacrol loaded nanoparticles were particularly active against planktonic forms and that the antibiofilm activity was highly dependent on the species tested, with the C. tropicalis and C. krusei strains resulting as the most susceptible.

Formulation and Characterization of Chitosan Based Dexibuprofen Nanoparticles Using Ionotropic Gelation Method

Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID), which is used to treat pain and inflammation. Like common NSAIDs, Dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. The therapeutic use of Dexibuprofen is limited by the rapidity of the onset of its action and its short biological half-life. Hence, our aim was to develop Dexibuprofen nanoparticles formulation to overcome these disadvantages using optimized concentration of polymers by appropriate methods for nanoparticle preparation. The drug and the nanoparticle formulation of Dexibuprofen F11 were comparatively assessed for FT IR spectrums by using FT-IR method. The DSC study was used as one of the tool to assess the compatibility between drug and the excipients. As per DSC thermograms, the drug as well as drug with mixture of excipients chitosan, sodium tripolyphosphate had shown no interactions with dexibuprofen. The ionotropic gelation method was used to prepare Dexibuprofen nanoparticles. The chitosan and sodium tripolyphosphate (TPP) of different concentrations were used as polymers to prepare Dexibuprofen nanoparticles. Total eleven different formulations were explored with different concentrations of drug : polymer ratios using ionotropic gelation method to identify optimal concentrations of polymer. Among different formulations, F11 formulation with optimized concentration of 5% chitosan and 1% Sodium tripolyphosphate polymers along with Dexibuprofen showed maximum drug release. The objective was to evaluate the developed Dexibuprofen nanoparticles. In-vitro drug release was evaluated in 0.05M phosphate buffer pH7.2 and found that the drug release of F11 formulation of Dexibuprofen nanoparticle had shown release till 24 hours more than that of other trials. Hence, F11 formulation was considered as the optimized nanoparticle formulation to control drug release till 24 hours. The entrapment efficacy of the formulated Nanoparticles was found to be in the range of 75.48%-91.22% respectively.

Preparation, Evaluation & Optimization of Nanoparticles Composed of Pyridostigmine

The purpose of this study was to prepare Pyridostigmine nanoparticles for control release of Pyridostigmine to improve the oral bioavailability, enhance the solubility and dissolution rate by decreasing particle size of drug. Infrared spectroscopic studies confirmed that there was no interaction between drug and polymers. The controlled release Pyridostigmine nanoparticles were prepared by Solvent evaporation by using Ethyl cellulose, Chitosan & HPMC K100 at different ratios. The production yield of the formulated controlled release nanoparticles (F1 to F16) in the range of 76.11 % to 83.58 %. The drug content of the formulated controlled release nanoparticles (F1 to F16) in the range of 82.56 %to 98.20%. The Theoretical loading of the formulated controlled release nanoparticles (F1- F16) in the range of 24.43 % to 64.24%. The entrapment efficiency increased with increasing the concentration of polymers and the formulations containing chitosan nanoparticles F6 (1:2) showed better entrapment (90.94%) among all formulation. The solubility of selected formulation (F6) in 0.2 M Phosphate buffer pH 6.8 increased when compared to pure drug. Particle size distribution was determined by Malvern zeta size, the size range for produced nanoparticles in the range of 200 nm to 400 nm. The Polydispersity index of selected nanoparticle formulation (F6) was indicated a narrow range and a homogeneous size distribution of particles. The in vitro dissolution study was carried out in 0. 2N PBS for 2 hours and phosphate buffer pH 6.8 for 10 hours. The formulations shows controlled release of drug up to 12 hrs and all formulations showed more than 75% of drug release. The release kinetics showed that the formulations were complies with Zero order kinetics followed by diffusion controlled mechanism. The best formulation F6 was evaluated by infrared spectroscopy, particle size, Polydispersity index & zeta potential and Scanning Electron microscopy. Best formulation of nanoparticles shown the extent of drug release was found to be F6 (96.93%) in 12 hrs. SEM studies confirmed the morphology of the nanoparticle formulation. Keywords: Polydispersity index, Zeta potential, Scanning Electron microscopy, Pyridostigmine

Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety.

DDRE-35. PRE-CLINICAL ASSESSMENT OF PPRX-1701, A NANOPARTICLE FORMULATION OF 6-BROMO-ACETOXIME, FOR THE TREATMENT OF GLIOBLASTOMA

We previously showed that derivatives of the Chinese traditional medicine indirubin promote survival in murine glioblastoma models (Williams et al. Cancer Research 2011). However, poor drug solubility hampered further development of this approach. Here we introduce PPRX-1701, a 6’-bromoindirubin acetoxime (BiA) containing drug/polymer nanoparticle formulation which can be injected intravenously at relatively high concentrations. Mechanistically, BiA is thought to act as a broadly selective serine-threonine protein kinase inhibitor, with activity against Src family kinases, GSK-3 and JAK2. Our preliminary data show that intravenous administration of PPRX-1701 is well-tolerated and can reach intracranial murine glioblastoma as assessed by luminescent reporter assays. PPRX-1701 administration leads to improved survival in the GL261 glioblastoma mouse model (median survival 30 days (control), 47 days (treated), p < 0.0001). Treatment with PPRX-1701 was associated with alterations in the tumor immune microenvironment, with reduced Tregs and pro-tumor macrophages, and increased CD8+ T cells. Further preliminary mechanistic studies have shown that PPRX-1701/BiA blocks the expression multiple immunosuppressive molecules in GBM downstream of interferon-g (IFNg) including PD-L1 and indoleamine 2,3-dioxygenase 1 (IDO1) - a key enzyme in the tryptophan–kynurenine–aryl hydrocarbon receptor (Trp–Kyn–AhR) immunosuppressive pathway. BiA promoted more effective T-cell mediated tumor cell killing using patient derived glioblastoma ex vivo co-culture models. This data supports further development of PPRX-1701 is a candidate immunotherapeutic agent for glioblastoma treatment. Ongoing pre-clinical studies are investigating combination with other relevant therapies.

Application of Plackett-Burman design for screening of factors affecting pitavastatin nanoparticle formulation development

Introduction: Nanoparticle formulation of pitavastatin calcium is a potential alternative to solve the solubility related problem. However, the formulation of nanoparticle involves various parameters that affect product quality. Plackett-Burman design could facilitate an economical experimental plan that focuses on determining the relative significance of many. Aim: The objective of this study was to screen the variables which could significantly affect the pitavastatin nanoparticle formulation. Materials and methods: The pitavastatin nanoparticles were formulated by preparing nanosuspension using the emulsion solvent evaporation technique followed by freeze-drying. A Plackett-Burman screening design methodology was employed in which seven factors at two levels were tested at 12 runs to study the effect of formulation and process variables on particle size and polydispersity index of nanoparticles. The surface morphology and crystalline nature of nanoparticle were also evaluated. Results: The particle size and polydispersity index of nanosuspension was found in the range of 113.1 to 768.5 nm and 0.068 to 0.508, respectively. Statistical analysis of various variables revealed that stabilizer concentration, injection flow rate, and stirring rate were the most influential factors affecting the particle size and polydispersity index of the formulation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) study suggested the amorphous nature of nanoparticles. Conclusions: This study concluded that the Plackett-Burman design was an efficient tool for screening the process and formulation variables affecting the properties of pitavastatin nanoparticles and also for the identification of the most prominent factor.

Curcumin: Its Bioavailability and Nanoparticle Formulation: A Review

Curcumin is used as traditional Indian and Chinese medicine in order to treat various diseases as well as used as a wound healing agent. Two to five percent in turmeric is curcumin; turmeric is available in yellow colour mainly obtained from polyphenolic pigment and fat-soluble substance called as curcuminoids, mostly used in the Indian subcontinent. Various clinical trials are conducted for understanding the wide range of therapeutic uses of curcumin. According to the studies, it shows that curcumin manifests very poor oral bioavailability, and forms numerous curcumin metabolites are formed after metabolism, although the bioavailability is low but the therapeutic activity of the curcumin for the various diseases, and for treatment of the disease enhancement of bioavailability of the curcumin in the future is necessary. According to the recent study on nanocurcumin with the size less than 100 nm which is an application of polymer-based nanoparticle of curcumin. It was observed that this polymer-based nanoparticle of curcumin has similar in vitro activity as that of free curcumin in pancreatic cell lines. In in-vivo study performed with the healthy volunteers a cream containing curcuminoid loaded SLNs was topically applied over the cream containing free curcuminoid showed the improvement in efficacy. Therefore, various techniques are developing for the nanoparticulate formulations. Key words: Curcuminoids, bioavailability, nanoparticulate, nanocurcumin, polyphenolic.

Nanoparticulate drug delivery systems: A revolution in design and development of drugs

The recent developments in nanoparticle-based drug formulations have been helping to address issues around treating challenging diseases. Nanoparticles come in different sizes but usually vary between 100nm to 500nm. For the past few years there has been research going on in the area of drug delivery using particulate delivery systems. Various drug molecules have been modified for both pharmacokinetic and pharmacodynamic properties using nanoparticles as physical approach. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. Here, we review various aspects of nanoparticle formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules and therapeutic genes. Keywords: nanoparticles, applications in delivery, Liposomes, Dendrimers

Nanoparticles eluting stents for coronary intervention: Formulation, characterization and in vitro evaluation

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles. The nanoparticle formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed nanoparticle formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed nanoparticle formulation was coated on the FlexinniumTM ultra-thin cobalt-chromium alloy coronary stent platform. The nanoparticle coated stents were characterized for morphology and residual solvent analysis. In-vitro drug release was also evaluated. Ex-vivo arterial permeation was carried out to evaluate the nanoparticle uptake from the surface of the stents. The characterization studies together corroborated that the developed nanoparticle coated stent can be a promising replacement of the current drug-eluting stents.