Nanoprecipitation Technique Research Articles

Direct preparation of drug-loaded mesoporous silica nanoparticles by sequential flash nanoprecipitation

The present work demonstrates how drug-loaded mesoporous silica nanoparticles (MSNPs) can be prepared by a sequential flash nanoprecipitation (FNP) technique. A sequential FNP technique is developed relying on a combination of two multi-inlet vortex mixers (MIVM), by which a continuous process that involves the formation of micelle-based templates followed by an in situ formation of MSNPs is achieved. Moreover, a widely used biological nematicide, abamectin (Abm), is added during the formation of micelles, ultimately leading to Abm-loaded MSNPs with high encapsulation efficiency. The obtained Abm-loaded MSNPs show excellent stability and inhibition activity against the livability of Meloidogyne incognita. Importantly, the parameters of the resulting MSNPs, such as silica shell thickness and inner cavity size of MSNPs, can be easily controlled by tuning the compositions of the reactant streams. We believe that such a simple approach towards direct preparation of drug-loaded MSNPs would find promising up-scale applications in various fields, such as drug delivery, bioimaging, and formulation technology.

Polycaprolactone based nano-carrier for co-administration of moxifloxacin and rutin and its In-vitro evaluation for sepsis

Clinically, complicated intra-abdominal infections (cIAIs) covers a broad spectrum peritonitis to acute appendicitis mainly associated with perforations in ischemic bowel. Antibiotics involved in treatment of cIAIs, possibly involved in pathophysiological initiation of sepsis by destructing the cell wall of microorganism and liberation of lipopolysaccharides (LPS) from bacterial cell. The present work is designed for fabrication of polycaprolactone (PCL) nanoparticles (NPs) for delivery of moxifloxacin (MOX) as antibiotic and rutin (RT) as adjuvant co-administered using PCL by nano-precipitation technique, followed by lyophilisation and In-vitro evaluation in J774 cell line. Preparation of polymeric NPs was by using certain modifications in nano-precipitation technique and certain process parameters were optimized. Stable NPs were then analysed for In-vitro cell line studies. Stable NPs had 173.63 nm ± 3.90 mean particle size, 0.107 ± 0.004 polydispersity, −22.63 ± 0.55 mV zeta potential, 7.49 ± 0.31% and 72.64 ± 1.06% drug loading and entrapment efficiency and sustained In-vitro release for 48 h. Antimicrobial activity of free MOX and PCL NPs of MOX against E. coli had correlation with In-vitro release studies. Cell viability studies on J774, THP1 and RAW 264.7 cell lines at various concentrations of PCL loaded NPs had more than 96.0% of cell viability. Cell uptake studies on J774 cell line confirmed phagocytosis mechanism of prepared PCL loaded nanoparticles. In-vitro cell line studies concluded that PCL loaded NPs of MOX and RT are safer for administration and In-vitro cellular uptake studies have provided a brief on potential of NPs for cellular uptake.

Programmable Hierarchical Construction of Mixed/Multilayered Polysaccharide Nanocapsules through Simultaneous/Sequential Nanoprecipitation Steps.

We report here on a one-pot construction of oil-filled hierarchical capsular assemblies using the nanoprecipitation technique. Relying on multicomponent phase diagrams, we show that simultaneous and/or sequential nanoprecipitations involving polymer combinations can be precisely programmed to design a new class of mixed/multilayered multicomponent nanocapsules, with a precise control of the dimensions, shell thickness/composition, and spatial distribution of the building blocks. The simplicity and tunability of this approach are exemplified here with a library of neutral and ionic polysaccharides giving access to a range of functional multilayered nanocarriers of interest for biomedical applications.

PEGylation of shellac-based nanocarriers for enhanced colloidal stability

Shellac is a biomaterial obtained from secretion of lac insects. Nanoparticles based on shellac are prepared by nanoprecipitation and miniemulsion techniques. The corrosion inhibitor 2-mercaptobenzothiazole can be efficiently encapsulated in nanoparticles. Release kinetics of the inhibitor from the nanocarriers is controlled by pH of the surrounding environment as well as the introduction of other biopolymers such as lignin and zein. To overcome the low colloidal stability of shellac nanoparticles in saline conditions, shellac is conjugated with poly(ethylene glycol) moieties. After PEGylation, nanoparticles with higher critical aggregation concentration are obtained and provide release kinetics of 2-mercaptobenzothiazole similar to shellac nanoparticles.

In vitro evaluation of folate-modified PLGA nanoparticles containing paclitaxel for ovarian cancer therapy.

Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.

Oxidation-Sensitive Dextran-Based Polymer with Improved Processability through Stable Boronic Ester Groups.

Particulate immunotherapy holds promise to vaccinate or treat a broad array of illnesses, including cancer, infectious diseases, and autoimmune disorders. The rate of antigen release from nano/microparticles (MPs) can impact both the type and quality of the immune response they elicit. The lysosomes of antigen-presenting cells are highly oxidizing. Thus, an oxidation-sensitive vehicle could enable a significant advancement in effective MP immunotherapy. One promising class of materials being developed toward this end is aryl-boronate-modified dextran polymers. The boronic esters used for oxidation-sensitive materials and sensors are typically made using pinacol (Pin) as a diol. However, Pin-based aryl-boronate-modified polymers are capable of transesterifying with biogenic diols, which can lead to undesirable interactions and poor material properties. To solve this, pinanediol (PD) was used in place of Pin in the synthesis of an aryl-boronate-modified dextran polymer (PDB-Dex), yielding a highly stable boronic ester. This modified dextran reverses its water solubility as desired, and improves on Pin-based materials by maintaining its solubility in organic solvents. MPs could be prepared by emulsion, nanoprecipitation, and electrospray techniques. The hydrogen peroxide-triggered degradation of microparticles was quantified colorimetrically, and the mechanism was probed using 1H NMR. Preliminary in vitro studies show low cytotoxicity and the ability to deliver an immunostimulatory agent.

Natural drug physcion encapsulated zeolitic imidazolate framework, and their application as antimicrobial agent

In this study, we have encapsulated natural physcion (PHY) drug loading into metal-organic frameworks MOFs, zeolitic imidazolate frameworks (ZIFs) through straight-forward nano-precipitation technique. The synthesized PHY@ZIF-8 indicated high drug loading encapsulation efficiency i.e. 88%, whereas, drug loading capacity was found to be 11.49%. The characterization of PHY loaded-ZIF 8 (PHY@ZIF-8) was carried out by powder x-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and FT-IR methods. The release of PHY loaded in ZIF-8 was 88.72% at pH 5.0 which is approximately three time higher than its release in physiological system with pH 7.4 (27.61%). The remarkable stability of PHY@ZIF-8 NPs even after 25 days stem it as an effective and stable candidate. Furthermore, the antibacterial activity of pure PHY, ZIF-8 and PHY@ZIF-8 were investigated against gram negative strains and gram positive strain. The PHY@ZIF-8 showed maximum growth inhibition zones against all microorganism as compare to pure PHY. We hope that this model drug could have the potential ability for treatment of various infectious diseases.

The crucial role of macromolecular engineering, drug encapsulation and dilution on the thermoresponsiveness of UCST diblock copolymer nanoparticles used for hyperthermia

Poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)), an upper critical solution temperature (UCST)-type copolymer in water, was synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization and used as a macro-RAFT agent for the polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to yield amphiphilic diblock P(AAm-co-AN)-b-POEGMA copolymer. A series of copolymers with different AN content was obtained allowing to finely tune the UCST behavior (cloud point (Tt-UCST) from 35 to 78 °C). Addition of the POEGMA block did not modify the Tt-UCST regardless its Mn but provided a lower critical solution temperature behavior at high temperature. Nanoparticles were then formulated by the nanoprecipitation technique revealing that copolymers with higher Tt-UCST yield smaller, better-defined nanoparticles. Eventually, doxorubicin (Dox) was encapsulated into nanoparticles made from the copolymer having a Tt-UCST close to mild hyperthermia (~43 °C). Surprisingly, Dox encapsulation increased Tt-UCST and gave smaller nanoparticles as opposed to their unloaded counterparts. The dilution of the suspension also led to a decrease of Tt-UCST. No obvious hyperthermia effect was observed on the cytotoxicity of Dox-loaded nanoparticles. Our study highlighted the influence of macromolecular engineering, drug encapsulation and nanoparticle dilution on UCST behavior, important features often overlooked despite their crucial impact in the development of thermosensitive nanoscale drug delivery systems.

Active targeting carrier for breast cancer treatment: Monoclonal antibody conjugated epirubicin loaded nanoparticle

Targeted nanomedicine plays an essential role in cancer therapy by delivering the drug to the malignant tumor cells directly. In this study, one of the potent anthracyclines, epirubicin (EPI), has been encapsulated in PLGA nanoparticles (NPs) conjugated by trastuzumab, as a monoclonal antibody (mAb). NPs was prepared by using nanoprecipitation technique. Characterizations have been performed by means of PCS, SEM, FT-IR and DSC techniques and then the optimum nanoparticles have been conjugated to mAb by an amide linkage.The results of the NPs preparation method showed the percentage yield of more than 90.55 ± 10.50% and entrapment efficiency of 91.05 ± 8.75%. PCS results showed that the average size of prepared NPs is approximately 74.66 ± 9.29 nm and 141 ± 58.41 nm for unconjugated and conjugated NPs respectively and a monodisperse distribution of them has been depicted by SEM micrograph.In vitro cellular experiments on overexpressing human epidermal growth factor receptor 2 (HER2) positive and negative cell lines demonstrated that mAb conjugated EPI-NPs has more cytotoxicity and drug uptake on over-expressed HER2 receptor cells in comparison to HER2 negative ones.The results of the current study have been demonstrated that targeted nanotechnology based formulations of EPI exhibit superior anticancer activity and have enormous potential in breast cancer (BC) treatment.

Development of transferrin-modified poly(lactic-co-glycolic acid) nanoparticles for glioma therapy.

Glioma is a primary intracranial malignant tumor with poor prognosis. In this study, we aimed to develop transferrin (Tf)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles to deliver temozolomide (TMZ) to glioma and evaluate their efficacy to kill glioma. TMZ-loaded nanoparticles were prepared by nanoprecipitation technique and targeted by Tf. Tf-PLGA-TMZ and PLGA-TMZ were characterized for average particle sizes and zeta potentials, cellular uptake and cytotoxicity as well as in-vitro drug release of these nanoparticles were evaluated in human glioma U87MG cells. In-vivo antiglioma efficacy of Tf-PLGA-TMZ was evaluated in nude mice. Polydispersity ratio increased from 0.132 to 0.150, while encapsulation efficiency decreased from 69.4 to 55.8% after Tf modification of PLGA-TMZ. High performance liquid chromatography test showed that Tf-targeted nanoparticles were better internalized into U87MG cells than nontargeted nanoparticles. Moreover, Tf-PLGA-TMZ significantly decreased the viability of U87MG cells compared with nontargeted nanoparticles (P<0.05). In addition, Tf-PLGA-TMZ significantly decreased tumor volume and improved the survival of nude mice injected with U87MG cells. Tf-modified PLGA nanoparticles could be used for effective delivery of TMZ and have promise for the treatment of glioma.

Optimization of the Single Emulsion Method for Encapsulation of a Cancer Drug in Nanoparticles.

The goal of this study is to apply and optimize the single emulsion technique for encapsulation of an anti-tumor drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), as a step towards targeted delivery of this drug. We previously showed that the nanoprecipitation technique can effectively produce PLGA NPs carrying this drug. Here, we aim to examine the single emulsion technique as an alternative for the preparation of these NPs and to compare the resultant NPs to those from nanoprecipitation. We fabricated NPs with variations in (i) injection rate, (ii) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (iii) concentration of PLGA in the organic phase. These NPs were characterized for size, surface potential, and encapsulation efficiency. The results revealed that increasing the injection rate (from manual addition to 90 mL/hr via syringe pump) greatly reduced the size of NPs (by 48%) and decreasing the PVA concentration in the aqueous phase (from 5 to 1% w/v) further reduced the NP size (by 32%) to 329 nm. All tested NP formulations had negative surface potential, suggesting good colloidal stability for these NPs. Focusing on the optimal injection rate and PVA percentage, we found that reducing the concentration of PLGA, from 100 to 1 mg/mL, significantly reduced the NP size to 136 nm, which is close to the optimal range for cancer therapeutic delivery. NPs produced by this method had a high encapsulation efficiency of 77% for Dp44mT and reducing the PLGA concentration slightly lowered this value to 74%. Overall, these NPs were comparable to those produced by nanoprecipitation and can thus, serve as an effective alternative for delivery of Dp44mT to cancer cells.

Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model.

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × 21 factorial design was applied to obtain optimized nanocapsules. Optimal nanocapsules showed mean particle size of 171nm with lower polydispersity index indicating the production of monodispersed system and negative zeta-potential of - 37.6mV. Optimized nanocapsules showed high encapsulation efficiency of 83.4% with lower initial rapid release of 10% for first 2h and higher rapid cumulative release of 72% after 6h. The therapeutic activity of the prepared budesonide-loaded nanocapsules was evaluated using a rat colitis model. Disease activity score, macroscopical examination, blood glucose level, and histopathological assessment showed marked improvements over that free drug suspension. Obtained results demonstrate that the budesonide-loaded Eudragit S 100 nanocapsules are an effective colon-targeting nanosystem for the treatment of inflammatory bowel disease. Capryol 90 was found to be a successful, and even preferred, alternative to benzyl benzoate, which is commonly employed as the oil core of such nanocapsules.

Essential Oils-Loaded Polymer Particles: Preparation, Characterization and Antimicrobial Property.

In the last few years, essential oils (EOs) derived from plants have aroused great interest due to their well-known antimicrobial activity. Unfortunately, they present several limitations in their use, such as photosensitivity, temperature sensitivity, high volatility, and poor water solubility. The encapsulation technique represents a good solution to these problems and ensures protection of the functional properties of essential oils. In this work, bergamot essential oil (BEO) and sweet orange essential oil (OEO) loaded-Eudragit® RS 100 (EuRS100) nanoparticles (NPs) were prepared by using the nanoprecipitation technique. We obtained nanoparticles characterized by a mean diameter of 57 to 208 nm and a positive surface charge (39 to 74 mV). The antibacterial activity of the obtained systems against Escherichia coli was in vitro investigated. We demonstrated that both orange and bergamot essential oils were successfully encapsulated and our nanoparticles have good antibacterial activity. Finally, in order to evaluate the potential applicability of OEONps to prolong fresh orange juice shelf-life, survival of E. coli during a storage period of one week at 25 °C was investigated: Orange essential oil-loaded nanoparticles (OEONPs) have been able to prolong the orange juice shelf life.

Preparation and Biopharmaceutical Evaluation of Novel Polymeric Nanoparticles Containing Etoposide for Targeting Cancer Cells.

Polymeric nanoparticles are a promising novel drug delivery system and have advantages in cancer therapy. Etoposide is an anticancer agent that is used in the treatment of a variety of malignancies. The aim of the present study was to prepare and evaluate novel polymeric nanoparticles containing etoposide. A 32 full factorial design was used to study the effect of Eudragit EPO and Pluronic F-68 on the characterization of nanoparticle suspensions. The polymeric nanoparticles were prepared by nanoprecipitation technique. The prepared nanoparticles was evaluated by percentage yield, drug polymer compatibility using fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetric (DSC) analysis, drug content, entrapment efficiency, zeta potential, particle size, scanning electron microscopy, X-ray diffraction, in vitro drug release studies, kinetic modeling, stability studies, and in vivo animal studies. Response surface plots were studied, which were generated using PCP dissolution software. Scanning electron microscopic studies confirmed their porous structure with a number of nanochannels. The FTIR spectra showed the stable character of etoposide in a mixture of polymers and revealed the absence of drug-polymer interactions. The DSC study revealed that the drug was involved in complexation with nanoparticles. The average particle size of etoposide nanoparticles was in the range of 114.4 nm to 136.7 nm. The zeta potential values were attained to ensure good stability of nanosuspensions. In vitro release of the drug from nanoparticles follows the Peppas model and showed controlled release behavior for a period of 24 h. The optimized nanoparticles were subjected to stability studies at 4°C in a refrigerator and the most suitable temperature for storage of etoposide nanoparticles found. The average targeting efficiency of drug-loaded nanoparticles was 41.88±0.030% of the injected dose in the liver, 25.66±0.320% in the spleen 13.82±0.090% in the lungs, 4.52±0.300% in the kidney, and 4.18±0.490% in the brain. Etoposide loaded nanoparticles was found to be effective in sustained release.

PH-sensitive polymeric nanoparticles of quercetin as a potential colon cancer-targeted nanomedicine

Quercetin (QCT) is an abundant plant polyphenol with demonstrated efficacy in several diseases including colon cancer. Herein we have developed polymeric nanoparticles (NPs) of QCT based on the pH-sensitive polymer Eudragit® S100 to achieve colon pH-specific drug release following oral administration. NPs were prepared by the nanoprecipitation technique and showed a mean diameter of 66.8 nm and a partially negative surface charge of −5.2 mV. NPs contained on average 2.2% w/w QCT at an encapsulation efficiency of 41.8%. IR spectroscopy and differential scanning calorimetry (DSC) both revealed the presence of intermolecular interactions, most likely H-bonding, between QCT and Eudragit® S100, which likely contributed to drug loading. DSC also indicated that the drug was present in the NPs in an amorphous state, which was further confirmed by X-ray diffraction. In vitro release testing showed a delay in drug release in acidic pH, but complete release within 24 h at pH 7.2. A cytotoxicity assay was performed on CT26 murine colon carcinoma cells, where QCT-loaded NPs displayed significantly higher potency (IC50 = 0.8 μM) than free QCT (IC50 = 65.1 μM). Our findings present a promising nanomedicine for colon-targeted delivery of QCT in diseases such as colon cancer.

Cholate-modified polymer-lipid hybrid nanoparticles for oral delivery of quercetin to potentiate the antileukemic effect.

Background: Quercetin (QUE) shows a potential antileukemic activity, but possesses poor solubility and low bioavailability.Purpose: This article explored the bile salt transport pathway for oral deliver of QUE using cholate-modified polymer-lipid hybrid nanoparticles (cPLNs) aiming to enhance its antileukemic effect.Methods: QUE-loaded cPLNs (QUE-cPLNs) were developed through a nanoprecipitation technique and characterized by particle size, entrapment efficiency (EE), microscopic morphology and in vitro drug release. In vitro cellular uptake and cytotoxicity of QUE-cPLNs were examined on Caco-2 and P388 cells; in vivo pharmacokinetics and antileukemic effect were evaluated using Sprague Dawley rats and leukemic model mice, respectively.Results: The prepared QUE-cPLNs possessed a particle size of 110 nm around with an EE of 96.22%. QUE-cPLNs resulted in significantly enhanced bioavailability of QUE, up to 375.12% relative to the formulation of suspensions. In addition, QUE-cPLNs exhibited excellent cellular uptake and internalization capability compared to cholate-free QUE-PLNs. The in vitro cytotoxic and in vivo antileukemic effects of QUE-cPLNs were also signally superior to free QUE and QUE-PLNs.Conclusion: These findings indicate that cPLNs are a promising nanocarrier able to improve the oral bioavailability and therapeutic index of QUE.

Synthesis of docosahexaenoic acid-loaded silver nanoparticles for improving endothelial dysfunctions in experimental diabetes.

To investigate the ability of docosahexaenoic acid (DHA)-loaded silver nanoparticles (AgNPs) in facilitating the incorporation of DHA in the cell membrane, improve cell membrane structure, and attenuate endothelial dysfunction in experimental diabetes. DHA/AgNPs were prepared using a nanoprecipitation technique. Fifty male albino rats were used in this study; 10 of them were served as the control group and 40, as the experimental groups, were injected with streptozotocin. Then, the experimental groups were subdivided into diabetic, diabetic treated with DHA, diabetic treated with AgNPs, and diabetic treated with DHA/AgNPs groups. DHA/AgNPs have small spherical size as proved from ultraviolet-visible spectroscopy, transmission electron microscope, dynamic light scattering, and scanning electron microscope techniques. Cell membrane cholesterol and triglycerides showed a significant elevation in the diabetic group compared to the control, but treatment with DHA and DHA/AgNPs caused a significant reduction in both. Treatment with AgNPs and DHA/AgNPs caused a significant improvement in asymmetric dimethylarginine and nitric oxide levels compared to the diabetic group. Cell membrane fatty acids showed that omega-6 polyunsaturated fatty acids (PUFAs) were significantly elevated, while omega-3 PUFA were significantly reduced in the diabetic group compared to the control. There is a significant improvement in the levels of fatty acids in all groups after treatment with DHA, silver, or DHA/AgNPs. DHA/AgNPs are potent agents for the improvement of diabetic complication and endothelial dysfunction in experimental diabetes.

Nanosized and Enhancement of Solubility Fisetin

Fisetin (3,3,4,7-tetrahydroxyflavone) is a natural antioxidant that has shown to posses anticancer, antioxidant and anti-inflammatory properties. However, the poor solubility leads to poor bioavailability and limits its development.The aim of the research is to investigate the effect of fisetin nanosuspension using a nanoprecipitation technique and additional stabilizers polysorbat 80, SLS, PVA and Eudragit on particle size average, polydispersity index and zeta potential.The suspensions of microcrystalline FIS were prepared by a nanoprecipitation technique with different proportion of stabilizers fixed. The nanosuspension produced was then characterized using Photon Correlation Spectroscopy (PCS) in term of particle size distribution, polydispersity index, zeta potential and morphology nanosuspensiom (TEM). Result showed fisetin nanosuspension were successfully prepared by anti-solvent precipitation with additional stabilizer SLS and polysorbat 80. The nanosuspension containing polysorbat 80 showed smaller average particle size of 225.7 nm ± 1.31, a polydispersity index of 0.272 ±0.02 and zeta potential -39.3 ± 0.26 was obtained. Conclusion, FIS nanosuspension successfully prepared by nanoprecipitation tecnique with the polysorbate 80 as stabilizer and ethanol as solvent were spherical in shape..

Docetaxel-loaded lipid-polymer hybrid nanoparticles for breast cancer therapeutics

In spite of extensive research over the decades, breast cancer therapy is still a big challenge because of non-specific delivery of the chemotherapy agents and could be overcome by limiting the distribution of chemotherapeutic agents towards the cancer cells. The current study was designed to develop docetaxel (DTX) encapsulated lipid polymer hybrid nanoparticles (LPHNPs-DTX) for controlled and sustained delivery of this drug. LPHNPs-DTX were prepared by self-assembled nano-precipitation technique and characterized for particle size, zeta potential, PDI, entrapment efficiency and in-vitro drug release. The characterized formulations were used to evaluate cell viability, cellular uptake, apoptosis, pharmacokinetics, biodistribution in vital organs, % changes in tumor volume and animal survival. In-vitro cell studies showed better cytotoxicity and greater cellular uptake of docetaxel at lower IC50 in breast cancer cell lines. Further, improved apoptosis was estimated with Flow cytometry. Furthermore, in-vivo studies exhibited better pharmacokinetics and tumor targetability with the least drug distribution in various organs with LPHNPs-DTX as compared to free DTX. Moreover, a noticeable % reduction in tumor burden was observed with LPHNPs-DTX as compared to free DTX. Our studies with LPHNPs-DTX exhibited promising outcomes to advance therapeutic interventions to combat breast cancer.

Stabilization of bluish pyranoanthocyanin pigments in aqueous systems using lignin nanoparticles

Lignin nanoparticles (LNP) loaded with pyranoanthocyanin dimers (PD) and portisins (P) were produced using nanoprecipitation and dialysis techniques. The results obtained for LNP and P-LNP showed particles presenting sizes around 200 nm with a very narrow size distribution (PDI ≤ 0.2) using both methods. For PD-LNP, the nanoprecipitation method yielded particles with high particle sizes (Z-average ≈ 800 nm) and PDI ≈ 0.45 when compared to the dialysis method that produced particles with an average size around 200 nm and a PDI below 0.2. Concerning the average zeta potential (ζ), values around – 40 mV were obtained for both methods. TEM, SEM and STEM images showed that the particles present a spherical and compact shape and that these characteristics were maintained for 28 days at room temperature. High encapsulation efficiencies of 86 ± 2 and 85 ± 4 were observed for PD and P, respectively. LNP stability was followed at pH ≥ 5 for at least 7 days and the LNP encapsulated systems (PD-LNP and P-LNP) showed a good colour stability towards pH change after 8 days of incubation, when compared with the pure bluish pigments.