Nanoprecipitation Method Research Articles

All-in-One Theranostic Platforms: Deep-Red AIE Nanocrystals to Target Dual-Organelles for Efficient Photodynamic Therapy.

Aggregation-induced emission (AIE) nanoparticles have been widely applied in photodynamic therapy (PDT) over the past few years. However, amorphous nanoaggregates usually occur in their preparation, resulting in loose packing with disordered molecular structures. This still allows free intramolecular motions, thus leading to limited brightness and PDT efficiency. Herein, we report deep-red AIE nanocrystals (NCs) of DTPA-BS-F by following the facile method of nanoprecipitation. It is observed that DTPA-BS-F NCs possess not only a high photoluminescence quantum yield value of 8% in the deep-red region (600-850 nm) but also an impressive reactive oxygen species (ROS) generation efficiency of up to 69%. Moreover, DTPA-BS-F NCs targeting dual-organelles of lysosomes and nucleus to generate ROS are also achieved, thus boosting the PDT effect in cancer therapy both in vitro and in vivo. This work provides high-performance AIE NCs to simultaneously target two organelles for efficient photodynamic therapy, indicating their promising application in all-in-one theranostic platforms.

Effect of curcumin-loaded photoactivatable polymeric nanoparticle on peri-implantitis-related biofilm

Curcumin has been used as a photosensitizer (PS) for antimicrobial photodynamic chemotherapy (PACT). However, its low solubility, instability, and poor bioavailability challenge its in vivo application. This study aimed to synthesize curcumin-loaded polymeric nanoparticles (curcumin-NP) and determine their antimicrobial and cytotoxic effects. Nanoparticles (NP) were synthesized using polycaprolactone (PCL) as a polymer by the nanoprecipitation method. Curcumin-NP was characterized by particle size, polydispersity index and zeta potential, scanning electron microscopy, and curcumin encapsulation efficiency (EE). Curcumin-NP was compared to free curcumin solubilized in 10% DMSO as photosensitizers for PACT in single and multispecies Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus oralis biofilms. Chlorhexidine 0.12% (CHX) and ultrapure water were used as positive and negative controls. The cytotoxic effect of curcumin-NP was evaluated on human periodontal ligament fibroblast cells (HPLF). Data were analyzed by ANOVA (α=0.05). Curcumin-NP exhibited homogeneity and stability in solution, small particle size, and 67.5% EE of curcumin. Curcumin-NP presented reduced antibiofilm activity at 500 µg/ml, although in planktonic cultures it showed inhibitory and bactericidal effect. Curcumin-NP and curcumin with and without photoactivation were not cytotoxic to HPLF cells. Curcumin-NP has antimicrobial and antibiofilm properties, with better effects when associated with blue light, being a promising therapy for preventing and treating peri-implant diseases.

Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.

Tuning of (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene nanostructures for the selective detection of imidacloprid

The present work demonstrates a facile route for synthesizing the organic nanoparticles (ONPs) and the blue fluorescent Quantum Dots (QDs) based on an organic molecule named (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene. The synthesis process possesses advantages viz green synthesis, non-toxic degraded products, and amount of organic compound. Initially, the ONPs were prepared using the nanoprecipitation method and were screened for their recognition potential against various pesticides, however, no selectivity has been observed. This motivated us to tune the ONPs into QDs. The QDs were prepared using the hydrothermal method and a color change was observed in the QDs solution under daylight and under a UV lamp. The emission wavelength was observed at 400 nm (λexcitation = 278 nm). The synthesized QDs exhibited selective sensing potential towards imidacloprid via a quenching mechanism. A normalised decrement in the luminescence intensity of QDs was observed on raising the concentration of imidacloprid and a good linear response was noticed over a concentration varies from 1 μM to 100 μM with a regression coefficient of 0.99. The detection limit was estimated to be 4.53 nM and quantification limit was calculated to be and 13.72 nM.

Formulation and characterisation of Azadirachta indica nanobiopesticides for ecofriendly control of wheat pest Tribolium castaneum and Rhyzopertha dominica

This study aimed to formulate the green, sustainable, and ecofriendly nanobiopesticides of Azadirachta indica with enhanced pest control efficacy. Nanoprecipitation method was used for the development of nanobiopesticides. Optimisation was done by response surface methodology. Nanoformulations were characterised by zetasizer, scanning electron microscopy, energy dispersive x-ray spectroscopy, atomic force microscopy, and Fourier transform infrared spectroscopy. Pesticidal potential of nanosuspensions was evaluated by insecticide impregnated filter paper method. Optimised nanobiopesticide showed an average particle size of 275.8 ± 0.95 nm, polydispersity index (PDI) 0.351 ± 0.002, and zeta potential of –33 ± 0.90 mV. Nanobiopesticides exhibited significantly higher mortality rates of 86.81 ± 3.04 and 84.97 ± 2.83% against Tribolium castaneum and Ryzopertha dominica, respectively, as compared to their crude extract. Minor change in particle size from 275.8 ± 0.95 to 298.8 ± 1.00 nm and PDI from 0.351 ± 0.002 to 0.445 ± 0.02 were observed after 3 months of storage at 4 °C. Pesticidal efficacy of A. indica was significantly enhanced by the formulation of its nanobiopesticides.

Flash nanoprecipitation enables regulated formulation of soybean protein isolate nanoparticles

Soy protein isolate (SPI) is perspective building block for fabrication of cargo-loaded nanoparticles (NPs) based on different formulation strategies. Particularly, precipitation demonstrates an easy and widespread fabrication approach, whereas most of the reported precipitation methods rely on spontaneous aggregation of SPI which typically suffers from the poor control on particle size and limited drug loading capacity. Herein, we reported a flash nanoprecipitation (FNP) method for regulated formulation of lutein-loaded SPI NPs. Specifically, solvent streams containing SPI and lutein are mixed with anti-solvent streams in a multi-inlet vortex mixer. Different control factors including lutein/SPI mass ratio and flow rate are investigated, and the obtained lutein-loaded SPI NPs show regulated particle size (80–122 nm), narrow size distribution (PDI ∼ 0.2), enhanced drug loading content (20%), high stability and improved bioaccessibility of lutein up to 94%. All these desirable properties are related to the kinetically trapped state of NPs due to the rapid mixing of FNP, which shall be hardly achieved with conventional precipitation approaches. Along with other intrinsic features such as fast mixing and continuous production, FNP possesses distinctive advantages for efficient fabrication of drug-loaded SPI NPs with regulated size and properties which are favorable for diverse delivery applications.

Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA.

Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon.

Carrier-free supramolecular nanoassemblies of pure LSD1 inhibitor for effective anti-tumor therapy.

The LSD1 protein is an oxidase that regulates protein methylation, which regulates gene expression and triggers tumors. Previously, inhibiting LSD1 has been found to be an effective treatment strategy for opposing tumors caused by overexpression of LSD1. Our recent study found that compound 17i was a suitable LSD1 inhibitor with potential anti-tumor activity. However, its extremely insoluble nature limits further validation of its anti-tumor activity at the clinical level. In this study, a unique carrier-free supramolecular nanoassemblies of pure compound 17i is expected to enhance therapeutic efficacy. Aqueous-insoluble compound 17i was mixed with a small quantity of DSPE-PEG2000 into an organic solvent and was prepared as nanoassemblies in water via the one-step nanoprecipitation method. The 17i nanoassemblies have a similar effect on its cytotoxicity when compared with 17i solution in vitro. Importantly, the PEGylated 17i nanoassemblies exhibit significant superiorities over 17i solutions in therapeutic efficiency, anti-tumor immune response and systemic toxicity in BALB/c mice bearing CT-26 colorectal tumors. We envision that the fabrication of pure drug nanoassemblies offers an efficient platform for reforming the undesirable characteristics of drug-like compounds to potentiate the anti-tumor therapeutic effect.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

Effect of Nanoparticles of DOX and miR-125b on DNA Damage Repair in Glioma U251 Cells and Underlying Mechanisms.

Glioma is the most common primary craniocerebral malignant tumor, arising from the canceration of glial cells in the brain and spinal cord. The quality of life and prognosis of patients with this disease are still poor. Doxorubicin (DOX) is one of the most traditional and economical chemotherapeutic drugs for the treatment of glioma, but its toxic effect on normal cells and the resistance of tumor cells to DOX make the application of DOX in the treatment of glioma gradually less effective. To solve this problem, we co-encapsulated DOX and endogenous tumor suppressor miR-125b into nanoparticles (NPs) by nanoprecipitation methods, and passively targeted them into glioma cells. In vitro experiments show that miR-125b and DOX can be effectively encapsulated into nanoparticles with different ratios, and by targeting YES proto-oncogene 1 (YES1), they can affect the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/p53 pathway and induce brain glioma cell apoptosis. They can also affect the DNA damage repair process and inhibit cell proliferation. The obtained data suggest that co-delivery of DOX and miR-125b could achieve synergistic effects on tumor suppression. Nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

Preparation of Black pepper (Piper nigrum L.) essential oil nanoparticles and its antitumor activity on triple negative breast cancer in vitro.

The active compounds isolated from Black pepper have anticancer effects, but the bioactivity of Black pepper essential oil (BP-EO) is rarely studied. BP-EO has poor stability and a suitable dose form should be prepared for in vivo delivery. Triple negative breast cancer (TNBC) has attracted more and more attention due to its high mitotic index, high metastasis rate and poor prognosis. In this study, the composition of BP-EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and nanoparticles (NPs) loaded with BP-EO were prepared by nanoprecipitation method using Eudragit L100 as a carrier. We investigated the preparation, characterization, stability and in vitro release of nanoparticles. MTT assay, cell wound healing, Transwell invasion assay and Western blot were used to study the anti-tumor effect and mechanism of MDA-MB-231 cells. The GC-MS analysis identified a total of 33 compounds among which alkenes account for 63.55%. The prepared BP-EO NPs exhibited nanoscale morphology, good stability and pH-responsive and sustained release character which is suitable for in vivo delivery. BP-EO NPs significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells. Furthermore, BP-EO NPs significantly inhibited the expressions of Wnt and β-catenin and significantly activated the expression of GSK-3β in MDA-MB-231 cells. Therefore, BP-EO NPs prepared in this study provide a new effective strategy for the treatment of TNBC. PRACTICAL APPLICATIONS: Black pepper is rich in essential oil and has excellent antioxidant and antibacterial activities. However, the anti-tumor activity of BP-EO has not been studied. In this study, we found that BP-EO has excellent anticancer activity. To achieve effective encapsulation of black pepper essential oil and an excellent anti-triple negative breast cancer activity, nanoparticles loaded with BP-EO were prepared using Eudragit L100 as the carrier by the nanoprecipitation method. The in vitro study revealed that BP-EO NPs inhibited proliferation, migration and invasion of MDA-MB-231 cells via inhibiting the Wnt/β-Catenin signaling pathway. This study provides new ideas and innovations for the treatment of invasive triple negative breast cancer in the future. At the same time, we will further reveal the application potential, pharmacokinetic characteristics and precise mechanism of BP-EO NPs in vivo in subsequent studies.

Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery of Peganum harmala smoke extract to breast cancer cells

In this study, PLGA-NPs coated with folic acid-chitosan (PCF-NPs) loaded with Peganum harmala smoke extract (PSE) were synthesized (PSE-PCF-NPs), and their anti-cancer effects were evaluated. PSE-PCF-NPs were synthesized by the nanoprecipitation method and then characterized by DLS, SEM, and FTIR methods. HPLC and UV–vis spectroscopy were used to evaluate the PSE’s folic acid (FA) binding and encapsulation. PSE-PCF-NPs-mediated cell viability and apoptosis were investigated by MTT, qPCR, flow cytometry, AO/PI, and DAPI staining. Anti-oxidant properties of PSE-PCF-NPs were evaluated by ABTS, DPPH, FRAP, and ROS. Angiogenic effects of PSE-PCF-NPs were assessed by CAM assay. The PSE-PCF-NPs (276.16 nm, PDI: 0.25, zeta-potential: +32.31 mV, FB: 67.6% and %EE: 89%) demonstrated selective toxicity on MCF-7 cells (IC50: 75.65 μg ml−1). The occurrence of apoptosis in MCF-7 cells was confirmed by up-regulation of P53, Cas-3, and Cas-9 genes, increased SubG1 phase cells, and the results of fluorescent staining. Scavenging free radicals, reducing iron ions, increasing intracellular ROS, and decreasing SOD gene confirmed the anti- and pro-oxidant effects of PSE-PCF-NPs outside and inside MCF-7 cells. Reduction of angiogenic factors in CAM assay showed the anti-angiogenic effects of PSE-PCF-NPs. PSE-PCF-NPs, due to their anti-cancer properties, can be considered a therapeutic agent in cancer studies.

Dimethylaminoethyl Methacrylate/Diethylene Glycol Dimethacrylate Grafted onto Folate-Esterified Bagasse Xylan/Andrographolide Composite Nanoderivative: Synthesis, Molecular Docking and Biological Activity.

As a biocompatible biomaterial, bagasse xylan (BX) has been widely used in the biomedical field. The low biological activity of andrographolide (AD) restricts its development, so AD with certain anticancer activity is introduced. We use chemical modification methods such as grafting and esterification to improve the biological activity and make a novel anticancer nanomaterial. On the basis of the esterification of a mixture of BX and AD with folic acid (FA), a novel anticancer nanoderivative of bagasse xylan/andrographolide folate-g-dimethylaminoethyl methacrylate (DMAEMA)/diethylene glycol dimethacrylate (DEGDMA) nanoparticles (FA-BX/AD-g-DMAEMA/DEGDMA NPs) was synthesized by introducing DMAEMA and DEGDMA monomers through a graft copolymerization and nanoprecipitation method. The effects of reaction temperature, reaction time, the initiator concentration and the mass ratio of FA-BX/AD to mixed monomers on the grafting rate (GR) were investigated. The structure of the obtained product was characterized by FTIR, SEM, XRD and DTG. Further, molecular docking and MTT assays were performed to understand the possible docking sites with the target proteins and the anticancer activity of the product. The results showed that the GR of the obtained product was 79% under the conditions of the initiator concentration 55 mmol/L, m (FA-BX/AD):m (mixed monomer) = 1:2, reaction temperature 50 °C and reaction time 5 h. The inhibition rate of FA-BX/AD-g-DMAEMA/DEGDMA NPs on human lung cancer cells (NCI-H460) can reach 39.77 ± 5.62%, which is about 7.6 times higher than that of BX. Therefore, this material may have potential applications in the development of anticancer drug or carriers and functional materials.

Evaluation and characterization of starch nanoparticles for adsorption of urea from dialysates

Starch nanoparticles (SNPs) was produced from type-A, B and C native starches (corn, potato and Trichosanthes kirilowii pulp starches respectively), via the nanoprecipitation method. The SNPs showed different amylose contents, water contact angles, surface morphologies and urea clearance performances. In this work, to examine the parameters of SNPs that may change the urea adsorption capacity, urea adsorption performance in adsorption environments with different pH values, urea concentrations, and adsorption times was examined. Thereafter, the characteristics of SNPs were tested by water contact angle measurements (WCA), transmission electron microscopy, specific surface area measurements, gel permeation chromatography, and zeta potential analysis. The results showed that the Trichosanthes kirilowii pulp (C) SNPs show better adsorption than the corn (A) and potato (B) SNPs. The hydrophobicity of SNPs promotes the urea adsorption of the SNPs. Using grey relational analysis, it was found that WCA and Mn are the critical parameter affecting the adsorption performance, with WCA and Mn within the ranges of 31–33° and 1900–2100 kDa, respectively, were found to be the conditions for optimal urea adsorption.

An electrochemiluminescence biosensor based on morphology controlled iridium complex nanomaterials for SARS-CoV-2 nucleocapsid protein detection

The morphology of electrochemiluminescence (ECL) emitters is closely related to ECL properties, thus the control of their morphology is greatly essential for ECL applications. Herein, a facile nanoprecipitation method was developed to realize controllable morphology of iridium complex nanomaterials by modulating the volume ratio of poly(styrene-co-maleicanhydride) (PSMA) to tris (2-phenylpyridine) iridium(Ⅲ) (Ir(ppy)3). Furthermore, ECL properties of iridium complex nanomaterials with different morphologies were explored through a series of experiments. Iridium complex nanoparticles (Ir NPs) with excellent ECL performance were selected as admirable ECL emitters to construct biosensors. Ir NPs served as the matrix to stepwise capture primary antibody, antigen of SARS-CoV-2 nucleocapsid protein (ncovNP) and secondary antibody bioconjugate coupled with dual quenchers and detection antibody. Taking advantage of the significant quenching effect of noradrenaline (NA) and gold nanoparticles (Au NPs) in the secondary antibody bioconjugate on ECL emission from Ir NPs, the developed ECL biosensor realized the sensitive detection of ncovNP and the detection limit was as low as 47 fg/mL. The integration of morphology-controlled iridium complex nanomaterials and dual quenchers NA and Au NPs provides a promising ECL platform.

Alpha-Mangostin-Loaded Transferrin-Conjugated Lipid-Polymer Hybrid Nanoparticles: Development and Characterization for Tumor-Targeted Delivery.

Alpha-mangostin, a natural xanthone mainly extracted from the pericarp of Garcinia mangostana, has been shown to have promising anticancer properties in many types of cancer. However, the therapeutic potential of α-mangostin has been limited so far due to its poor aqueous solubility and low oral bioavailability, which limited its biopharmaceutical applications. Furthermore, α-mangostin failed to specifically reach tumors at a therapeutic concentration due and rapid elimination in vivo. We hypothesized that this drawback could be overcome by loading the drug within a delivery system conjugated to transferrin (Tf), whose receptors are overexpressed on many cancer cells and would enhance the specific delivery of α-mangostin to cancer cells, thereby enhancing its therapeutic efficacy. The objectives of this study were therefore to prepare and characterize transferrin-conjugated lipid-polymer hybrid nanoparticles (LPHN) entrapping α-mangostin, as well as to evaluate their therapeutic efficacy in vitro. We successfully prepared α-mangostin loaded LPHN using a one-step nanoprecipitation method with high drug entrapment efficiency. The conjugation of Tf to the LPHN was achieved by using the thiol–maleimide “click” reaction, leading to an increase in the particle hydrodynamic size of Tf-LPHN compared to that of unconjugated (control) LPHN (Ctrl-LPHN). Both Tf-LPHN and Ctrl-LPHN were bearing negative surface charges. Tf-LPHN and Ctrl-LPHN exhibited a sustained release of α-mangostin at pH 7.4, following an initial burst release, unlike rapid release of drug solution. The entrapment of α-mangostin in the LPHN led to an increase in α-mangostin uptake by cancer cells, and thus improved its antiproliferative activity compared to that observed with the drug solution. In conclusion, α-mangostin entrapped in the Tf-LPHN is therefore a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment.

Preparation, Characterization, and Biological Evaluation of a Hydrophilic Peptide Loaded on PEG-PLGA Nanoparticles.

The encapsulation of peptides and proteins in nanosystems has been extensively investigated for masking unfavorable biopharmaceutical properties, including short half-life and poor permeation through biological membranes. Therefore, the aim of this work was to encapsulate a small antimicrobial hydrophilic peptide (H-Ser-Pro-Trp-Thr-NH2, FS10) in PEG-PLGA (polyethylene glycol-poly lactic acid-co-glycolic acid) nanoparticles (Nps) and thereby overcome the common limitations of hydrophilic drugs, which because they facilitate water absorption suffer from rapid degradation. FS10 is structurally related to the well-known RNAIII inhibiting peptide (RIP) and inhibits S. aureus biofilm formation. Various parameters, including different method (double emulsion and nanoprecipitation), pH of the aqueous phase and polymeric composition, were investigated to load FS10 into PEG-PLGA nanoparticles. The combination of different strategies resulted in an encapsulation efficiency of around 25% for both the double emulsion and the nanoprecipitation method. It was found that the most influential parameters were the pH—which tailors the peptides charge—and the polymeric composition. FS10-PEG-PLGA nanoparticles, obtained under optimized parameters, showed size lower than 180 nm with zeta potential values ranging from −11 to −21 mV. In vitro release studies showed that the Nps had an initial burst release of 48–63%, followed by a continuous drug release up to 21 h, probably caused by the porous character of the Nps. Furthermore, transmission electron microscopy (TEM) analysis revealed particles with a spherical morphology and size of around 100 nm. Antimicrobial assay showed that the minimum inhibitory concentration (MIC) of the FS10-loaded Nps, against S. aureus strains, was lower (>128 µg/mL) than that of the free FS10 (>256 µg/mL). The main goal of this work was to develop polymeric drug delivery systems aiming at protecting the peptide from a fast degradation, thus improving its accumulation in the target site and increasing the drug-bacterial membrane interactions.

Enhancing cellular uptake and membrane permeability of gallic acid for breast cancer therapy via folate-tagged PEGylated iron oxide nanoparticles has theronastic agent

BackgroundIn an attempt to prove biological activity enhancement upon escalating the cellular uptake response through ligand and carrier-based via nanoframework, gallic acid was chosen to be formulated into PLGA-based polymeric nanoparticles with iron oxide as the theranostic agent.ResultsThe pre-formulation studies like FTIR, DSC, XRD, and TGA were carried out, which implies good compatibility between drug and polymer. Furthermore, the nanoparticles were prepared by using a single nanoprecipitation method, and the prepared nanoparticles were optimized using the Box–Behnken design. This design was used to optimize the gallic acid-loaded PEGylated nanoparticles by considering the effects of three factors (X1; lipid, X2; PLGA, and X3; drug) on the response variables Y1 (EE), Y2 (size), and Y3 (drug release). The findings of surface response plots are attributed to an optimized nanoparticle. The in vitro drug release followed a biphasic release profile in both tested media, pH 4.8 and 7.4. The desirable physicochemical characteristics involved small particle size with considerable stability, which was attained due to the anionic nature of PLGA. The in vitro cytotoxicity assay of gallic acid, GA/PLGA-IONPs, and optimized FA-GA/PLGA-PEGylated-LIONPs were evaluated using the MTT assay, which showed an inhibition effect on MCF-7 cells to induce apoptosis. Cellular uptake and fluorescence studies show higher cellular uptake and destruction of cells based on concentration dependence.ConclusionsThe above results show that prepared nanoparticles sustain the therapeutic concentration of the drug on target cells by enhancing permeability through the PEGylated lipid delivery system.

Formulation and evaluation of nano-particulate topical gel containing Celecoxib

The present research work describes formulation and evaluation of celecoxib containing gel using transdermal delivery. Transdermal potential of nanoparticulate gel was investigated using in-vitro and in-vivo study. In present study procured drug samples were investigated under preformulation studies. For development of nanparticles containing celecoxib, nanoprecipitation method is used. The formulated nanoparticles were evaluated for different parameters such as zeta potential, particle size, % entrapment efficiency, in-vitro drug release, SEM and stability studies. The formulated nanoparticles were formulated as gel using carbopol. Formulated carbopol gels were characterized for appearance, spreadability, pH, viscosity, drug content, consistency index and ex-vivo drug release, in-vitro drug release. Formulated gels were evaluated for in-vitro studies (skin irritation and skin permeation). Further evaluated for stability studies as per ICH guidelines, results of stability studies reveled that both the formulated gels were found to be stable at stuied temperatures.

Osteopontin-Targeted and PPARδ-Agonist-Loaded Nanoparticles Efficiently Reduce Atherosclerosis in Apolipoprotein E–/– Mice

Atherosclerosis is the leading cause of vascular pathologies and acute cardiovascular events worldwide. Early theranostics of atherosclerotic plaque formation is critical for the prevention of associated cardiovascular complications. Osteopontin (OPN) expression in vascular smooth muscle cells (VSMCs) has been reported as a promising molecular target for the diagnosis and treatment of atherosclerotic plaques. The PPARδ agonist GW1516 has been shown to inhibit VSMC migration and apoptosis. However, GW1516 has low aqueous solubility and poor oral bioavailability, which are major obstacles to its broad development and application. In this study, GW1516@NP-OPN, which is anti-OPN-targeted and loaded with the PPARδ agonist GW1516, was synthesized using a nanoprecipitation method. The uptake of GW1516@NP-OPN was examined using fluorescence microscopy and flow cytometry assay in VSMC in vitro models. Using the Transwell assay and acridine orange/ethidium bromide staining methods, we observed that the inhibition of VSMCS migration and apoptosis was significantly higher in cells treated with GW1516@NP-OPN than those treated with free GW1516. The western blot assay further confirmed that GW1516@NP-OPN can increase FAK phosphorylation and TGF-βprotein expression. The effect of NPs was further tested in vivo. The atherosclerotic lesion areas were greatly decreased by GW1516@NP-OPN compared with the free drug treatment in apolipoprotein E–/– mice models. Consequently, our results showed that GW1516@NP-OPN stabilizes the PPARδ agonist aqueous formulation, improves its anti-plaque formation activities in vivo and in vitro, and can therefore be recommended for further development as a potential anti-atherosclerotic nanotherapy.