Nanoprecipitation Technique Research Articles

Development and characterization of erythrosine nanoparticles with potential for treating sinusitis using photodynamic therapy

Antimicrobial therapy for sinusitis has been shown to reduce or eliminate pathologic bacteria associated with rhinosinusitis and improve the symptoms associated with the disease. However, the continuing rise in antibiotic resistance, the ongoing problem with patient compliance, and the intrinsic difficulty in eradication of biofilms complicates antibiotic therapy. The introduction of photodynamic antimicrobial therapy (PAT) using erythrosine, a photosensitizer, could eliminate the bacteria without inducing antibiotic resistance or even requiring daily dosing. In the present study, erythrosine nanoparticles were prepared using poly-lactic-co-glycolic acid (PLGA) and evaluated for their potential in PAT against Staphylococcus aureus cells. PLGA nanoparticles of erythrosine were prepared by nanoprecipitation technique. Erythrosine nanoparticles were characterized for size, zeta potential, morphology and in vitro release. Qualitative and quantitative uptake studies of erythrosine nanoparticles were carried out in S. aureus cells. Photodynamic inactivation of S. aureus cells in the presence of erythrosine nanoparticles was investigated by colony forming unit assay. Nanoprecipitation technique resulted in nanoparticles with a mean diameter of 385nm and zeta potential of -9.36mV. Erythrosine was slowly released from nanoparticles over a period of 120h. The qualitative study using flow cytometry showed the ability of S. aureus cells to internalize erythrosine nanoparticles. Moreover, erythrosine nanoparticles exhibited a significantly higher uptake and antimicrobial efficacy compared to pure drug in S. aureus cells. In conclusion, erythrosine-loaded PLGA nanoparticles can be a potential long term drug delivery system for PAT and are useful for the eradication of S. aureus cells.

Curcumin-Loaded Chitosan-Coated Nanoparticles as a New Approach for the Local Treatment of Oral Cavity Cancer

Mucoadhesive nanoparticles loaded with curcumin were developed as a new approach to deliver curcumin for the local treatment of oral cancer. PCL nanoparticles coated with chitosan displaying different molar masses were prepared by using the nanoprecipitation technique. The mucoadhesive properties of nanoparticle suspensions were demonstrated by their strong ability to interact with the glycoprotein mucin through electrostatic interactions. Similar permeation profiles of curcumin loaded in uncoated and chitosan-coated nanoparticles across porcine esophageal mucosa were verified. Curcumin concentrations retained in the mucosa suggest the possibility of a local effect of the drug. In vitro studies demonstrated that free curcumin.and curcumin loaded into nanoparticles coated with chitosan caused significant reduction of SCC-9 human oral cancer cell viability in a concentration and time-dependent manner. However, no significant cell death was observed after 24 h of treatment with unloaded nanoparticles coated with chitosan. In addition, curcumin-loaded nanoparticles showed reduced cytotoxicity, when compared with the free drug. Therefore, chitosan-coated PCL nanoparticles may be considered a promising strategy to deliver curcumin directly into the oral cavity for the treatment of oral cancer.

Solvent selection causes remarkable shifts of the "Ouzo region" for poly(lactide-co-glycolide) nanoparticles prepared by nanoprecipitation.

Polymer nanoparticles (NPs) offer versatile novel biological features of interest for drug delivery applications. "Ouzo diagrams" allowed for a systematic manufacture of specified colloidal formulations by the widely used nanoprecipitation process. Surprisingly, despite the well-documented relevance of the applied organic solvent for nanoprecipitation, its effect on the actual status of the "Ouzo region" was so far not studied. Herein, investigations were undertaken to account for the potential impact of the solvent type on the "Ouzo diagrams" for poly(lactide-co-glycolide) (PLGA) and tetrahydrofuran (THF), 1,4-dioxane, acetone and dimethyl sulfoxide (DMSO). The "Ouzo region" shifted considerably to higher polymer fractions upon solvent change (rank order: THF < 1,4-dioxane < acetone < DMSO). Assuming a one-to-one transformation of detached PLGA-bearing solvent droplets (droplet diameter for THF: ∼800 nm, 1,4-dioxane: ∼700 nm, acetone: ∼500 nm and DMSO: ∼300 nm) into non-divisible polymer aggregates upon solvent displacement, facilitated to predict the size of NPs found within the "Ouzo region" (size range: 40-200 nm). In conclusion, application of "Ouzo diagrams" is a valuable tool for drug delivery research and will most-likely replace the "trial-and-error"-approach to identify the operating window for the production of stable colloidal formulations by the nanoprecipitation technique.

Elaboration of Nanoparticles Containing Indomethacin: Argan Oil for Transdermal Local and Cosmetic Application

The objective of this work is the preparation of nanocapsules which are intended for the treatment of rheumatoid arthritis (RA). We use Argan oil as vehicle of hydrophobic drugs such as indomethacin. Nanoprecipitation technique was used like a method for preparation of nanocapsules, where polycaprolactone, acetone, and Argan oil are used as polymer, solvent, and carrier, respectively. Primarily, investigation of Argan oil amount addition was performed; then systematic study to optimize the formulation was done. Nanocapsules containing indomethacin (loaded nanocapsules) and others without indomethacin (blank nanocapsules) were characterized by studying particles size, zeta potential, and encapsulation efficiency. It is shown that particle size ranged between 290 nm and 350 nm. The zeta potential values were negative (from −40 up to −50 mV) while encapsulation efficiency ranged between 65 and 75%.

Utilization of Crosslinked Starch Nanoparticles as a Carrier for Indomethacin and Acyclovir Drugs

An eco-friendly nanoprecipitation technique was put forward to synthesize native starch nanoparticles loaded with insoluble drugs such as indomethacin (IND) and Acyclovir (ACV). Factors studied to find out the optimum conditions for preparation of different formulations of crosslinked starch nanoparticles (TPP-StNPs) loaded with insoluble drugs. The factors are 20 mg, 50 mg of drug concentration and 0.5, 1 g of sodium tripolyphosphate (STPP) while the concentration of starch and surfactant were kept constant. World-class facilities as particle size analyzer, poly dispersity index (PDI), zeta potential, TEM, XRD, FT-IR, UV-vis spectroscopy and DSc were used for evaluation of the resultant crosslinked starch nanoparticles loaded with drug. The sustained release of drugs were evaluated using entrapment efficiency and in vitro release. The data obtained confirmed that there is no chemical interaction between drug (IND, ACV) and crosslinked starch nanoparticles. The results indicate that the best formula for IND loaded starch nanoparticles was 0.5 g STPP and 20 mg IND while the best formula for ACV nanoparticles was at 0.5 g STPP and 50 mg ACV drug.

Formulation and Characterization of Nateglinide Nanosuspension by Precipitation Method

Poor water solubility and slow dissolution rate are major issues for the majority of upcoming and existing biologically active pharmaceutical compounds. Nateglinide is Biopharmaceutical Classification System Class-II drug that has low solubility and high permeability. The purpose of the present study was to improve the solubility and dissolution rate of Nateglinide by the preparation of nanosuspension by the nanoprecipitation technique. Nateglinide nanosuspension was evaluated for its particle size, in vitro dissolution study, and characterized by differential scanning calorimetry and scanning electron microscopy. The optimized formulation showed an average particle size of 207 nm and zeta potential of -25.8 mV. The rate of dissolution of the optimized nanosuspension was enhanced by 83% in 50 min relative to micronized suspension of nateglinide (37% in 50 min). This improvement was mainly due to the formulation of nanosized particles of Nateglinide. Stability study revealed that nanosuspension was more stable at room temperature and refrigerator condition with no significant change in particle size distribution. These results indicate that the nateglinide loaded nanosuspension may significantly improve in vitro dissolution rate and thereby possibly enhance the onset of therapeutic effect.

Sterically stabilized polymeric nanoparticles with a combinatorial approach for multi drug resistant cancer: In vitro and in vivo investigations

The present work describes the preparation of sterically stabilize polymeric nanoparticles of mitoxantrone dihydrochloride (MTO) along with an efflux transporter (Pgp/BCRP) inhibitor that enhance the circulation time of nanoparticles and simultaneously surmount the problem of multidrug resistance (MDR). Mitoxantrone dihydrochloride being hydrophilic in nature had very low entrapment efficiency (%E.E.), thus in order to further enhance the lipophilicity and the %E.E., it was complexed with sodium deoxycholate (SDC) and this MTO-SDC-complex was used to formulate nanoparticles with/without Pgp/BCRP inhibitor by nanoprecipitation technique and was characterized for various in vitro and in vivo attributes. In vitro cell line studies were conducted on MCF7, A2780(p) and A2780(adr) cells. Furthermore, the targeting potential of hyaluronic acid (HA) coated nanoparticles for CD44 receptors was investigated using the MCF7 cell line. A reduction in the IC50 value observed with the inhibitor loaded nanoparticles in different cell lines indicated the BCRP/Pgp inhibiting ability of the formulated nanoparticles. The reduced macrophage uptake and the increased residence time in blood demonstrated the long circulating behaviour of the nanoparticles. The enhanced cellular uptake of HA coated nanoparticles in MCF7 cells revealed their targeting potential. The HA coated nanoparticles along with efflux transporter inhibitor exhibits a great potential for targeted chemotherapy in CD44 overexpressing MDR breast cancer.

A new formulation of curcumin using poly (lactic-co-glycolic acid)—polyethylene glycol diblock copolymer as carrier material

The aim of this study is to fabricate a nanoparticle formulation of curcumin using a relatively new vehicle as the matrix polymer: poly(lactic-co-glycolic acid) (PLGA)- polyethylene glycol (PEG) diblock copolymer, and to investigate the effects of the various processing parameters on the characteristics of nanoparticles (NPs). We successfully synthesized the matrix polymer of PLGA-PEG by conjugation of PLGA copolymer with a carboxylate end group to a heterobifunctional amine-PEG-methoxy using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide as conjugation crosslinkers. The composition of the formed product (PLGA-PEG) was characterized with 500 MHz 1H nuclear magnetic resonance (NMR). The conjugation of PLGA-PEG was confirmed using Fourier transform infrared (FTIR) spectrum study. This diblock copolymer was then used to prepare the curcumin-loaded NPs through nanoprecipitation technique. With this method, we found that the size distribution depends on the type of solvent, the concentration of polymer and the concentration of surfactant. The particle size and size distribution were measured by dynamic light scattering (DLS). Transmission electron microscope (TEM) and scanning electron microscope (SEM) were used to confirm the size, structure and morphology of the successfully prepared NPs. All of our results showed that they are spherical and quite homologous with mean diameter around of 100–300 nm. Further, we evaluated encapsulation efficiency and some characteristics of NPs through high performance liquid chromatography (HPLC) analyses, zeta-potential measurements and x-ray diffraction studies. The HPLC analyses were performed to determine the amount of curcumin entrapped in NPs. The zeta-potential measurements confirmed the stability of NPs and the successful encapsulation of curcumin within NPs and the x-ray diffraction patterns showed the disordered-crystalline phase of curcumin inside the polymeric matrix.

Development of Albendazole Nanosuspension by Various Techniques

Albendazole, an anthelmintic drug belonging to BCS class II, has poor bioavailability. Bioavailability is dissolution rate dependent and hence needs novel approach for enhancement of bioavailability. The aim of the study was to develop nanosuspension of albendazole by using various techniques like nanoprecipitation, emulsion template and sonication. Nanosuspensions were prepared using polyvinylpyrrolidone K30 as a stabilizer and Tween 80 as a surfactant. Average particle size, zeta potential, particle size distribution, pH, viscosity, photomicrography, sedimentation, redispersibility and % drug content were determined to characterize prepared nanosuspensions. In vitro release study was performed in 0.1N HCl using cellophane membrane and compared with marketed product. Residual solvent determination was carried out by gas chromatography for nanosuspensions prepared by nanoprecipitation and emulsion template techniques. All the results obtained for characterization were satisfactory. The prepared nanosuspensions showed particle size 673±9.18 nm to 893±21.6 nm, zeta potential -8.70±0.5mV to -8.96±0.8, polydispersity index 0.204±0.04 to 0.644±0.07. In vitro release study of the nanosuspensions showed 33.80% to 42.92% drug release in first hour which was higher than the marketed suspension (16.19% release in first hour). The optimized nanosuspensions showed up to 97.05 % drug release within 6-8 hours while marketed product showed up to 91.03% drug release within 10 hours. Keywords: Albendazole, bioavailability, dissolution, emulsion template, nanoprecipitation, sonication.

Synthesis and lectin recognition of glycosylated amphiphilic nanoparticles

Carbohydrate–protein interactions play an important role in many biomolecular recognition events and thus artificial glycopolymers and glycoparticles are actively developed. Nanoprecipitation and aerosol flow reactor techniques were used to prepare glucose-decorated nanoparticles capable of binding to lectin Concanavalin A (ConA). The nanoparticles were based on a polystyrene-block-polypentafluorostyrene (PS-b-PFS) block copolymer that was post-functionalised with glucose units via thiol para-fluorine click reaction to yield PS-b-PFS-GlcOH. Thus it was of interest to see how different methods of fabrication affect the particle size and, more importantly, the localization of the glucose units on the particle surfaces. Nanoprecipitation of the PS-b-PFS-GlcOH gave monodisperse particles with a mean diameter of 97nm, while the particles made with aerosol flow reactor had mean diameter of 357nm. For comparison, aerosol particles with mean diameter of 194nm were made from the starting polymer PS-b-PFS and these nanoparticles were further surface modified with glucose. With light scattering and fluorescence spectroscopy it was shown that all the prepared particles bind fluorescently labeled lectin Con A via multivalent binding between the glucose units of nanoparticles and the lectin. Fluorescence resonance energy transfer (FRET) was used to study the interaction of fluorescent moieties on sub-nanometer scale and used to quantify the efficiency of binding. The studies showed that all the glycosylated nanoparticles gave FRET effect, and, when compared to the glucose concentration, the surface modified nanoparticles gave the highest response.

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain

Context & Objective: The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug.Methods: Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study.Results: Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential −18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers.Conclusions: IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Size-controlled biodegradable nanoparticles: Preparation and size-dependent cellular uptake and tumor cell growth inhibition

Biodegradable nanoparticles with diameters below 1000nm are of great interest in the contexts of targeted delivery and imaging. In this study, we prepared PLGA nanoparticles with well-defined sizes of ∼70nm (NP70), ∼100nm (NP100), ∼200nm (NP200), ∼400nm (NP400), ∼600nm (NP600) and ∼1000nm (NP1000) using facile fabrication methods based on a nanoprecipitation and solvent evaporation techniques. The nanoparticles showed a narrow size distribution with high yield. Then the size-controlled biodegradable nanoparticles were used to investigate how particle size at nanoscale affects interactions with tumor cells and macrophages. Interestingly, an opposite size-dependent interaction was observed in the two cells. As particle size gets smaller, cellular uptake increased in tumor cells and decreased in macrophages. We also found that paclitaxel (PTX)-loaded nanoparticles showed a size-dependent inhibition of tumor cell growth and the size-dependency was influenced by cellular uptake and PTX release. The size-controlled biodegradable nanoparticles described in this study would provide a useful means to further elucidate roles of particle size on various biomedical applications.

Dual drug delivery of 5-fluorouracil (5-FU) and methotrexate (MTX) through random copolymeric nanomicelles of PLGA and polyethylenimine demonstrating enhanced cell uptake and cytotoxicity

We now report the synthesis of a random copolymer of poly-lactic-co-glycolic acid (PLGA) grafted branched polyethylenimine (BPEI) and the use of it as a multi drug delivery system (DDS). The methotrexate (MTX) was conjugated to BPEI through DCC/NHS chemistry. The copolymer–drug conjugate (PBP–MTX) was characterised by FT-IR and 1H NMR spectroscopy. The PBP–MTX was converted into nanomicelles with entrapped 5-fluorouracil (5-FU) through nanoprecipitation technique. The size, shape, morphology and surface charge of the nanomicelles were confirmed using different techniques. The thermal behaviour and distribution of both conjugated and entrapped drug through the polymeric matrix were assessed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). In vitro drug release pattern of the nanomicelles was examined to ascertain the release pattern of two drugs namely 5-FU and MTX. The cellular uptake studies demonstrated higher uptake of the nanomicelles in colon cancer cell line HCT 116. Further the cytotoxicity evaluation of nanomicelles illustrated promising action which confirms the use of the system as a potential DDS to colon cancer.

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

ABSTRACTDexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of −2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41199.

Protective efficacy of ursodeoxycholic acid nanoparticles in animal model of inflammatory bowel disease

Context: Ursodeoxycholic acid (UDCA) exerts dose-dependent chemoprevention in colonic inflammation. Polycationic UDCA nanoparticles (UNPs) are envisaged for solubility enhancement and site directed drug delivery. Objective: The objective was to study the ameliorative efficacy of UNPs through localized delivery of the drug. Methods: UNPs were prepared through nanoprecipitation technique. Particle size, morphology, in vitro drug release and in vivo protective efficacy in inflammatory bowel disease (IBD) of these nanoparticles were studied. Results and Discussion: The average particle size was around 100 nm, and the average drug encapsulation was about 99%. In vitro drug release study shows optimal drug release in simulated colonic fluid. The lowering of tissue nitric oxide, malondialdehyde, myeloperoxidase and histology of the colon tissue supported the protective efficacy of the nanoparticles. Conclusion: This study presents the improved efficacy of UNPs in animal model of IBD due to complete release of drug at the desired site of action.

Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems.

In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with 99mTc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12645-014-0003-9) contains supplementary material, which is available to authorized users.

Development of polymeric nanoparticles with highly entrapped herbal hydrophilic drug using nanoprecipitation technique: an approach of quality by design

The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2–7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 32 factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50 mM exhibited best EE (82.12%), PS (196.71 nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.

In vitro and in vivo analysis of the antithrombotic and toxicological profile of new antiplatelets N-acylhydrazone derivatives and development of nanosystems: Determination of novel NAH derivatives antiplatelet and nanotechnological approach

BackgroundCardiovascular diseases are the most frequent cause of morbidity and mortality worldwide. Among the most important cardiovascular diseases are atherothrombosis and venous thromboembolism that present platelet aggregation as a key event. Currently, the commercial antiplatelet agents display several undesirable effects, which prompt the search for new compounds with better therapeutic index, more efficient body distribution and mechanism. MethodsIn this work we characterized in vivo and in vitro the antithrombotic and toxicological profiles of novel antiplatelet N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides derivatives also comparing them with aspirin. In addition we also analyzed the stability of the more active compound after encapsulation in PLGA or PCL nanoparticles and the release profile of these new nanosystems. ResultsThe biological results revealed not only the selective effect against arachidonic acid-induced platelet aggregation mainly for compounds 2c, 2e and 2h but also their in vivo active profile on thromboembolism pulmonary animal model with better survival rates (e.g. 82%) than aspirin (33%). The overall toxicological profile was determined by in vitro (MTT reduction tests, neutral red uptake in kidney VERO cells and hemolysis assays) and in vivo (pulmonary embolism) assays that pointed 2c as the most promising derivative with potential as a lead compound. By using the nanoprecipitation technique 2c was loaded into PLGA and PCL nanoparticles showing controlled release profile over 21days according to our drug release tests. ConclusionAccording to our results compound 2c is the most interesting derivative for further studies as it showed the best activity and toxicological profile also allowing the nanoencapsulation process. Thus 2c may assist in determining a new potential therapy with favorable pharmacokinetics for treatment of thrombotic disorders.

Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells

Silibinin (SIL) is a plant derived flavonoid isolated from the fruits and seeds of the milk thistle (Silybum marianum). Silibinin possesses a wide variety of biological applications including anticancer activities but poor aqueous solubility and poor bioavailability limit its potential and efficacy at the tumor sites. In the present study, silibinin was encapsulated in Eudragit® E (EE) nanoparticles in the presence of stabilizing agent polyvinyl alcohol (PVA) and its anticancer efficacy in oral carcinoma (KB) cells was studied. Silibinin loaded nanoparticles (SILNPs) were prepared by nanoprecipitation technique and characterized in terms of size distribution, morphology, surface charge, encapsulation efficiency and in vitro drug release. MTT assay revealed higher cytotoxic efficacy of SILNPs than free SIL in KB cells. Meanwhile, reactive oxygen species (ROS) determination revealed the significantly higher intracellular ROS levels in SILNPs treated cells compared to free SIL treated cells. Therefore, the differential cytotoxicity between SILNPs and SIL may be mediated by the discrepancy of intracellular ROS levels. Moreover, acridine orange (AO) and ethidium bromide (EB) dual staining and reduced mitochondrial membrane potential (MMP) confirmed the induction of apoptosis with nanoparticle treatment. Further, the extent of DNA damage (evaluated by comet assay) was significantly increased in SILNPs than free SIL in KB cells. Taken together, the present study suggests that silibinin-loaded nanoparticles can be used as an effective drug delivery system to produce a better chemopreventive response for the treatment of cancer.

A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications.

Cyclodextrins (CDs) have brought a revolution in the pharmaceutical field over the last decade. Natural and modified CDs (α-CD and β-CD) have been studied and some have gained US FDA approval or achieved 'Generally Regarded as Safe' (GRAS) status. Another characteristic of CDs is the ease with which they can be induced to form supramolecular structures for its use in drug delivery. CDs, grafted or crosslinked with polymers, are now being developed into 'smart' systems for efficient targeted drug delivery, especially for hydrophobic drugs. Amphiphilic CDs have the ability to form nanospheres or nanocapsules via a simple nanoprecipitation technique. This review deals with different types of CDs, and their efficacy, physicochemical properties and transformation into nanoparticles with interesting in vitro and in vivo applications.