Narrow Polydispersity Index Research Articles

Formulation of Piperine-Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation.

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.

Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application.

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers.

BackgroundThe purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer.MethodsHePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo.ResultsThe average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced (P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs.ConclusionThese findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.

1-Ethyl-3-methylimidazolium acetate ionic liquid as simple and efficient catalytic system for the oxidative depolymerization of alkali lignin

The oxidative depolymerization of alkali lignin (AL) in 1-ethyl-3-methylimidazolium acetate ([C2C1im]OAc) system without additional catalyst was investigated under mild conditions (initial O2 pressure of 1.5 MPa, 80 °C–100 °C). Compared with other ionic liquids (ILs), the cooperation of imidazolium cation and acetate anion successfully enhanced AL conversion. Among the investigated imidazolium acetate ILs with ethyl- to octyl-side chains, [C2C1im]OAc presented the best catalytic capacity for AL oxidative depolymerization. Adding an appropriate amount of water to [C2C1im]OAc can further improve the reaction efficiency. In the [C2C1im]OAc system with the addition of 0.10–0.25 mL of water, approximately 77 wt% AL was depolymerized into small molecule soluble products at 100 °C for 2 h. The extracted oil was composed mainly of phenolic derived compounds. With the use of the [C2C1im]OAc-based system, the specific inter-unit linkages of lignin were broken down, and residual lignin with low molecular weight and narrow polydispersity index (1.88–1.96) was obtained. Compared with that in AL conversion with fresh [C2C1im]OAc, only a minimal decrease (~3.2%) was observed with the recovered IL until the fifth cycle. These findings revealed that [C2C1im]OAc–based system is a simple and efficient catalytic system for lignin oxidative depolymerization.

Clarithromycin Loaded Chitosan Nanoparticles: Development and Characterization

Background:: Chitosan nanoparticles have been extensively studied and used due to their well-recognized applicability in various fields. Chitosan, a natural polysaccharide polymer, is extensively used in pharmaceuticals to deliver a wide variety of therapeutic agents. Chitosan is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of multi particles, particularly nano- and microparticles. Objective:: The main aim of the present study was to optimize the conditions for the preparation of chitosan nanoparticles to get optimal particle size, with optimal zeta potential and narrow polydispersity index and anti-bacterial activity. Methods:: Include the ionic gelation technique for chitosan nanoparticle preparation. The influence of formulation parameters and process parameters on the chitosan nanoparticles were investigated. Besides, the suspension stability of the prepared nanoparticles was also assessed on storage at 4°C. Results: The formulation and process parameters showed a significant effect on the physicochemical and morphological characteristics of the chitosan nanoparticles. The chitosan nanoparticles prepared under optimum conditions (chitosan concentration of 0.5% w/v, CS: TPP mass ratio of 1:3, initial pH of chitosan solution of 4.5, stirred at 750 rpm for 30 min) had shown a mean particle size of ~326.8±15 nm, zeta potential of +28.2 ± 0.5 mV, and PDI of 0.21 ± 0.02. The encapsulation of the clarithromycin slightly increased the polydispersity index, but the zeta potential of the unloaded nanoparticles was not affected while the particle size increased. Under optimum conditions, clarithromycin encapsulation efficiency into nanoparticles was found to be 70%. Additionally, chitosan- tripolyphosphate nanoparticles were shown to be stable for a minimum of fifteen days in deionized water at 4°C. Conclusion:: The current study concludes the optimal conditions to formulate the chitosan nanoparticles with optimal physicochemical characteristics.

Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas.

Sarcomas are aggressive tumors which often show a poor response to current treatments. As a promising therapeutic alternative, we focused on mithramycin (MTM), a natural antibiotic with a promising anti-tumor activity but also a relevant systemic toxicity. Therefore, the encapsulation of MTM in nano-delivery systems may represent a way to increase its therapeutic window. Here, we designed novel transfersomes and PLGA polymeric micelles by combining different membrane components (phosphatidylcholine, Span 60, Tween 20 and cholesterol) to optimize the nanoparticle size, polydispersity index (PDI) and encapsulation efficiency (EE). Using both thin film hydration and the ethanol injection methods we obtained MTM-loaded transferosomes displaying an optimal hydrodynamic diameter of 100–130 nm and EE values higher than 50%. Additionally, we used the emulsion/solvent evaporation method to synthesize polymeric micelles with a mean size of 228 nm and a narrow PDI, capable of encapsulating MTM with EE values up to 87%. These MTM nano-delivery systems mimicked the potent anti-tumor activity of free MTM, both in adherent and cancer stem cell-enriched tumorsphere cultures of myxoid liposarcoma and chondrosarcoma models. Similarly to free MTM, nanocarrier-delivered MTM efficiently inhibits the signaling mediated by the pro-oncogenic factor SP1. In summary, we provide new formulations for the efficient encapsulation of MTM which may constitute a safer delivering alternative to be explored in future clinical uses.

Flexible Polyurethane Foams from Epoxidized Vegetable Oils and a Bio-Based Diisocyanate.

Bio-polyols from epoxidized soybean and linseed oils and caprylic acid or 3-phenyl butyric acid were prepared using an environmentally friendly, solvent-free method evaluating the presence of triethylamine as catalyst. Side reactions, leading to a cross-linking structure with high density, were reduced, introducing the catalyst and properly tuning the reaction conditions. A medium functionality value of around 3 along with a hydroxyl number up to around 90 mg KOH/g, narrow polydispersity index, and relatively low molecular mass up to 2400 g/mol were the experimental targets. From selected bio-polyols and an aliphatic partially bio-based isocyanate, a series of water blown polyurethane (PU) foams was produced, estimating the effect of the chemical nature of substituents in the polyol backbone on the PU properties. The apparent density of the foams was in the range of 79–113 kg/m3, with higher values for foams from the aromatic acid. Flexible polyurethane foams with open cell structure from bio-based polyols were obtained, with higher cavity size and lower pore sizes for foams from caprylic acid. The bio-based flexible PU foams showed comparable Young’s moduli (14–18 kPa) and compression deflection values (4.6–5.5 kPa) and exhibited an almost complete recovery of their initial size.

Development of oral aprepitant-loaded chitosan–polyethylene glycol-coated cyclodextrin nanocapsules: formulation, characterization, and pharmacokinetic evaluation

Aprepitant (APRT), a selective neurokinin 1 antagonist, is clinically used in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. The low solubility of APRT, which limits its oral bioavailability, is overcome by nanonization. This study aimed to design and evaluate novel in vitro and in vivo chitosan (CS)–polyethylene glycol (PEG)-coated cyclodextrin (CD) nanoparticles and nanocapsules to enhance the solubility and oral bioavailability of APRT. A novel amphiphilic CD derivative with alkyl chains of 9 carbons (ACD-C9) was synthesized to form nanoparticles and nanocapsules by using nanoprecipitation. The nanocarriers were coated with the CS–PEG conjugate to increase their biological interaction with cell membranes via the positive charge and penetration-enhancer properties of CS. The nanosystems were evaluated for particle size, surface charge, drug loading, imaging, release, cell culture, and oral bioavailability in an animal model. The CS–PEG-coated nanosystems had particle size of 400–550 nm, a narrow polydispersity index, positive zeta potential, and favorable drug loading (55 and 93% for nanoparticles and nanocapsules, respectively). Sustained release was observed within 24 h. Blank nanoparticles and nanocapsules were non-cytotoxic against the L929 cell line. The intestinal permeability of the nanocarriers was 2–threefold (2-3 fold) higher than that of the drug solution, and the nanocapsules afforded the highest APRT permeability through Caco-2 cells. Oral bioavailability studies in rats revealed comparable degree of drug absorption between nanocapsules and commercial APRT products. Oral ACD-C9 nanocapsules have the potential for the treatment of chemotherapy-induced nausea and vomiting.

Kinetics of MMA Atom Transfer Radical Polymerization Initiated by Reducing Agent in Stirred Batch Emulsion Reactor

AbstractAb initio emulsion atom transfer radical polymerization (ATRP) differs from regular emulsion polymerization because the kinetic and thermodynamic aspects of each process are very unlikely alike. This paper presents a kinetic analysis of activator generated by electron transfer (AGET) ATRP of methyl methacrylate (MMA) in a stirred emulsion reactor. The focus of the study is to assess the variation of the monomer content in the organic phase and the rate polymerization for different reaction temperatures, as well as the impact of surfactant content and stirring speed on latex stability. Poly(methyl methacrylate) (PMMA) polymer samples are analyzed by means of gravimetry, dynamic light scattering, gel permeation chromatography, and HNMR techniques to determine monomer conversion, polymer particle diameter, molecular weight distribution, and polymer molecular structure, respectively. The results show the production of PMMA of narrow polydispersity index (Ð) and low molar mass (Mn) for MMA conversion around 60% and detect two‐regions instead of a three‐regions trend of rate of polymerization (Rp) as conventional emulsion polymerization. The reaction rate increases during the nucleation stage and then flattens over an invariant trend which confirms a living feature of the AGET ATRP polymerization. The average number of radicals per latex particle (ñ) is also debated.

Well-controlled spiropyran functionalized polystyrenes via a combination of anionic polymerization and hydrosilylation for photoinduced solvatochromism

Si–H-functionalized polystyrene (PS–SiH) with a well-controlled molecular weight and narrow polydispersity index (PDI) was synthesized via anionic polymerization (AP) of (4-vinylphenyl)-dimethyl-silane (VPDMS), i.e., PVPDMS (Mn = 2.5 kg/mol, PDI = 1.16). Spiropyran (SP) derivatives as the photo-responsive function, i.e., SP-phenyl-Yne (M1) and SP-biphenyl-Yne (M2) bearing the same alkyne (Yne) terminals and different spacers (phenyl/biphenyl), were used to modify the resulting PVPDMS via hydrosilylation, affording SP-functionalized PSs (PVPDMS-SPM1/SPM2) with a defined number of SP attachments. The photoinduced solvatochromism of SP derivative small molecules and polymers was investigated in solvents of different polarities. The time-dependent conversion of different isomers was mainly qualitatively tracked by spectroscopic methods, allowing the transfer pathways among different SP isomers to be proposed. The appearance of trans-merocyanine (MC) H-aggregations was detected in the UV–Vis spectra of both SP derivative small monomers and polymers in relatively low-polarity solvents. Moreover, a discoloration process caused by the appearance of cis-MCs was observed under continuous illumination, which demonstrated that the appearance of aggregations and cis-MCs relied on the solvent polarity. More importantly, PVPDMS as the polymer backbone effectively decreased the rate of structural trans-to-cis MC conversion, indicating an inhibiting effect of the steric hindrance on the appearance of cis-MC molecules.

Progress in the Free and Controlled Radical Homo- and Co-Polymerization of Itaconic Acid Derivatives: Toward Functional Polymers with Controlled Molar Mass Distribution and Architecture.

Polymeric derivatives of itaconic acid are becoming increasingly more interesting for research and industry because itaconic acid is accessible from renewable resources. In spite of the structural similarity of poly(itaconic acid derivatives) to poly(methacrylates), they are much less reactive, homopolymerize only sluggishly by free radical polymerization (FRP), and are often obtained with low molar masses and conversions. This has so far limited their use. The reasons for the low reactivity of itaconic acid derivatives (including itaconimides, diitaconates, and diitaconamides) are combined steric and electronic effects, as demonstrated by the body of literature on the FRP homopolymerization kinetics of these monomers which is summarized herein. These problems can be solved to a large extent by using controlled radical polymerization (CRP) techniques, notably atom transfer radical polymerization (ATRP) and reversible addition and fragmentation chain transfer radical polymerization (RAFT). By optimizing the reaction conditions for the ATRP and RAFT of itaconic acid derivatives, in particular the reaction temperature, linear relations between molar mass and conversion are obtained in many cases, and homopolymers with high molar masses and reasonably narrow polydispersity indices become accessible. This review presents the state-of-the-art FRP and CRP of itaconic acid derivatives, and highlights functional polymers obtained by these methods.

Surface functionalisation of poly-APO-b-polyol ester cross-linked copolymers as core\u2013shell nanoparticles for targeted breast cancer therapy

Polymeric nanoparticles (NPs) are commonly used as nanocarriers for drug delivery, whereby their sizes can be altered for a more efficient delivery of therapeutic active agents with better efficacy. In this work, cross-linked copolymers acted as core–shell NPs from acrylated palm olein (APO) with polyol ester were synthesized via gamma radiation-induced reversible addition-fragmentation chain transfer (RAFT) polymerisation. The particle diameter of the copolymerised poly(APO-b-polyol ester) core–shell NPs was found to be less than 300 nm, have a low molecular weight (MW) of around 24 kDa, and showed a controlled MW distribution of a narrow polydispersity index (PDI) of 1.01. These properties were particularly crucial for further use in designing targeted NPs, with inclusion of peptide for the targeted delivery of paclitaxel. Moreover, the characterisation of the synthesised NPs using Fourier Transform-Infrared (FTIR) and Neutron Magnetic Resonance (NMR) analyses confirmed the possession of biodegradable hydrolysed ester in its chemical structures. Therefore, it can be concluded that the synthesised NPs produced may potentially contribute to better development of a nano-structured drug delivery system for breast cancer therapy.

Development, in vitro and in vivo evaluation of miltefosine loaded nanostructured lipid carriers for the treatment of Cutaneous Leishmaniasis.

The purpose of this study was to enhance the anti-leishmanial efficacy of miltefosine (MTF) and reduce its toxic effects by loading it into nanostructured lipid carriers (NLCs). Micro-emulsion technique was used to prepare MTF-loaded NLCs. The optimized NLCs were characterized in terms of various physicochemical parameters including particle size, poly dispersity index (PDI), zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) technique. In vitro and in vivo assays were performed to evaluate the potential of NLCs as an effective nanocarrier system for oral delivery of MTF in Cutaneous Leishmaniasis. The optimized MTF-loaded NLCs exhibited mean particle size of 160.8±5.3nm with narrow PDI and high incorporation efficiency (IE%) of 96.17±1.3%. MTF-loaded NLCs demonstrated slow release of the incorporated drug as compared to the drug solution. The optimized formulation showed significant decrease in hemolytic potential, 2.5~folds increase in anti-leishmanial efficacy and 6~fold decrease in macrophage cytotoxicity as compared to MTF solution, in vitro. Macrophage uptake study confirmed passive targeting ability of MTF-loaded NLCs. In-vivo analysis demonstrated enhanced anti-leishmanial effect of the MTF-loaded NLCs and better pharmacokinetic profiles with no gastrointestinal (GI) toxicity. NLCs are potential nanocarriers for the oral delivery of MTF with enhanced anti-leishmanial activity, better safety profile and reduced hemolytic potential.

Preparation and characterization of okara nanocellulose fabricated using sonication or high-pressure homogenization treatments

Nanocellulose was isolated from okara using either ultrasound or high-pressure homogenization treatments. Dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, swelling behavior, rheological properties, and thermal analysis were used to characterize the physical-chemical and structural properties of the cellulose obtained. Sonication at 600 W for 15 min led to a cellulose material with a small mean particle diameter (d =0.22 μm), narrow polydispersity index (PDI = 0.21), strong negative charge (ζ = −36 mV), high swelling ratio (SR = 7.6), high crystallinity index (CI = 72 %), and formed viscous solutions. The initial pyrolysis temperature of the cellulose increased from 212 to 225 ℃, while the pyrolysis residue decreased from 26 to 12 %, after the sonication/homogenization treatment. The cellulose material produced in this study may be applied in various food and non-food applications as a texture modifier, stabilizer, structural component, or digestion modifier.

PAMAM Dendrimer as a Talented Multifunctional Biomimetic Nanocarrier for Cancer Diagnosis and Therapy

Poly(amidoamine) dendrimers (PAMAM) are novel polymeric highly branched architectures with well-defined nano-size, narrow polydispersity index and numerous active amine functional groups at the periphery. The highly attractive feature of modifiable multiple surface functionalities facilitates conjugation of various ligands for cancer targeting, imaging and therapy. As well as, solubilization, high drug encapsulation, inherent passive targeting ability will also contribute to the therapeutic success of dendrimers. Cancer researchers are very eager about the utility of PAMAM dendrimer as a drug carrier and non-viral gene vector. This review highlighted the potential of non-targeted and ligand targeted surface engineered PAMAM dendrimers for the delivery of anticancer drugs and gene therapeutics and briefly focus on the diagnostic imaging applications of PAMAM dendrimers.

Process Optimization of Curcumin-Loaded Coconut Oil and Honey Nanoemulsion for Better Skin Permeation

This study was focused on the optimization of preparing a curcumin-loaded coconut oil and honey nanoemulsion using a low energy emulsifying technique. Curcumin is a bioactive compound with low bioavailability and stability. Response surface methodology (RSM) with Box Behnken design was used to optimize the base formulation based on the three independent variables such as honey (1–3%), virgin coconut oil (1.0–1.5%) and Tween 80 (5.0–9.0%) to obtain low particle size (10.11[Formula: see text]nm), polydispersity index (0.27) and turbidity (0.24–1.11) system. Subsequently, the second optimization was carried out after curcumin was loaded into the base formulation. Another three independent variables such as polyethelene glycol (0.8–1.5%), curcumin (0.01–0.1%) and honey (1.8–2.4%) were used to produce the nanorange of particle size (14.32[Formula: see text]nm), narrow polydispersity index (0.152), and high encapsulation efficiency (98.0%). The curcumin-loaded nanoemulsion was found to have high stability with only 8.5% increment in particle size after storage for three months at 4∘C and 45∘C. The radical scavenging activity of encapsulated curcumin in nanoemulsion was decreased ([Formula: see text]%) compared to free curcumin. Nanoemulsion appeared to increase in vitro release rate of curcumin by about 42%, especially for the first 2[Formula: see text]h in Franz diffusion cell using rat skin.

Amphiphilic AIE-active copolymers with optical activity by chemoenzymatic transesterification and RAFT polymerization: Synthesis, self-assembly and biological imaging

Recently, various AIE-based materials with new characteristics and functions have been developing for different fields. Many chiral polymers are attracting the research interests for the new multifunctional materials in biomedicine, chiral recognition, etc. In this work, novel AIE copolymers with chirality activity were successfully fabricated for the first time. Firstly, a new fluorescent monomer (R)-THM with AIE effect and chirality activity was firstly synthesized by Suzuki reaction and enzymatic transesterification reaction. The quantum yield of (R)-THM increased to 0.643 from 0.100 of its substrate TBP with remarkable red-shift of emission spectra, which was consistent with their quantum chemical calculations of HOMO and LUMO situations, and its specific optical rotation [α]D25°C was about −9.67°. Subsequently, a series of chiral AIE copolymers of PEG-(R)-THM1 and PEG-(R)-THM2 were prepared via RAFT polymerization of (R)-THM and PEGMA with different feeding ratios. Their molecular weights were about 2.0 × 104 g/mol with narrow polydispersity index (PDI), and the kinetics analysis presented a pseudo-first-order linear procedure. For the molar 24.2%–32.3% feeding ratio of (R)-THM, the actual fraction of (R)-THM in the copolymers PEG-(R)-THM1 and PEG-(R)-THM2 was respectively about 22.3% and 30.2%, and the [α]D25°C value of copolymers PEG-(R)-THM1 and PEG-(R)-THM2 was about −2.51° and −3.74°. The amphiphilic structure of the obtained PEG-(R)-THM make them be easily dispersed in water solution and tend to self-assemble into fluorescent organic nanoparticles (FONs) with 100–150 nm diameter by TEM, and their maximum emission wavelength presented at 495 nm with obvious AIE effect. Moreover, the PEG-(R)-THM FONs had good biological compatibility, desirable low cytotoxicity and good cells absorption effect, which showed the great potential in bioimaging application.

PHYSICOCHEMICAL CHARACTERIZATION OF QUERCETIN-LOADED LIPOSOMES PREPARED BY SONICATION FOR FUNCTIONAL FOOD APPLICATION

This research was intended to synthesize liposome as a nanocarrier to encapsulate quercetin, which is prone to degradation and susceptible to low bioavailability upon oral administration. The liposomes were synthesized by thin-film hydration method and followed by probe sonication for downsizing. Soy phosphatidylcholine (SPC) and cholesterol (CHOL) were employed as the composition of the phospholipid bilayer. Results indicated a dependence of sonication amplitude and time in the formation of free liposomes (FL). The average size of quercetin-loaded liposomes (QL) prepared was 346.4 nm with a narrow polydispersity index (0.22) and a high magnitude of zeta potential (-49.6 mV). These characterizations depict that a homogenous nanovesicle suspension with high stability was successfully synthesized. Quercetin was incorporated into the liposomes with a high encapsulation efficiency of 90.7% and loading capacity of 9.3%. This viable nanocarrier perhaps will provide ingenious protection for a wider spectrum of active agents in food and biopharmaceutical products.

DNA Polyplexes of a Phosphorylcholine-Based Zwitterionic Polymer for Gene Delivery.

We tested polyplexes of a diblock polymer containing a pH-responsive, endosomolytic core (dimethylaminoethyl methacrylate and butyl methacrylate; DB) and a zwitterionic Poly (methacryloyloxyethyl phosphorylcholine) (PMPC) corona for the delivery of plasmid DNA (pDNA) to glioblastoma cells. We studied the physicochemical characteristics of the DNA polyplexes such as particle hydrodynamic diameter and surface potential. Cytocompatibility of free PMPC-DB polymer and pDNA polyplexes with U-87MG and U-138MG glioma cell lines were evaluated using the ATP assay. The transfection activity of luciferase pDNA polyplexes was measured using a standard luciferase assay. Anti-proliferative, apoptotic, and cell migration inhibitory activities of PMPC-DB/Interferon-beta (IFN-β1) pDNA polyplexes were examined using ATP assay, flow cytometry, and wound closure assay, respectively. PMPC-DB copolymer condensed pDNA into nanosized polyplexes. DNA polyplexes showed particle diameters ranging from ca. 100-150nm with narrow polydispersity indices and near electroneutral zeta potential values. PMPC-DB/Luciferase pDNA polyplexes were safe and showed an 18-fold increase in luciferase expression compared to the gold standard PEI polyplexes in U-87MG cells. PMPC-DB/IFN-β1 polyplexes induced apoptosis, demonstrated anti-proliferative effects, and retarded cell migration in glioblastoma cells. The results described herein should guide the future optimization of PMPC-DB/DNA delivery systems for in vivo studies.

Abstract 2618: Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma

Abstract Targeted therapy in renal cell carcinoma (RCC) has limited clinical response due to the development of drug resistance. Drug resistance can be acquired through multiple pathways including, impairment of apoptosis, overexpression of hypoxia promoting carbonic anhydrase 9 (CA9), and infiltration of folate receptor (FR) positive tumorigenic macrophages. Our hypothesis was to overcome the drug resistance by developing a tumor stimuli-responsive nanoparticle (NP) that can carry combination drugs, such as Cabozantinib (CB) and CFM 4.16 in RCC. The rationale of choosing the CB in combination with CFM4.16 was to induce synergistic anti-RCC effect by modulating the multiple tumor survival pathways, such as caspase 3, Akt/p-Akt, MET. One of the major challenges of the CB and CFM4.16 combination therapy is their poor water solubility and limited targetability to cancer. Thus, we came up with a smart strategy of developing dual folate receptor (FR) and carbonic anhydrase-9 (CA9) biomarker directed nanoparticles that can target the tumor stroma and hypoxia of RCC, respectively. In this proof of concept study, we synthesized SMA-TPGS and SMA polymer (PL) comprising of FR and CA9 dual targeting ligand, namely, FR-CA9-OL using reagent free ‘click' chemistry. FR-CA9-PL was encapsulated either with CFM4.16 or with CB to obtain nanoparticles, called FR-CA9-C4.16 and FR-CA9-CB respectively. The nanoparticles were prepared by using a co-solvent dialysis method that resulted in small-particle size with a range of 80-100 nm diameter, narrow polydispersity index of ∼ 0.15 and high drug loading of 30% (wt./wt.). The homogenous and high drug loading characteristics of nanoparticles are optimal for penetrating hypoxia of RCC. The IC50 of FR-CA9-C4.16 was improved by 60-fold as compared to CFM4.16 treatment and IC50 of FR-CA9-CB is improved by 16-fold compared to CB treatment in aggressive Everolimus-resistant (Evr-res) A498 RCC cells. The combination of FR-CA9-C4.16 with FR-CA9-CB demonstrated synergistic killing of Evr-res-A498 with CI value 0.1-0.5. The signature characteristic and superior anticancer effect of nanoparticles in Evr-resistant RCC provide a worthwhile strategy for overcoming drug resistance in RCC. Citation Format: Kushal Vanamala, Samaresh Sau, Shivani Naik, Arun K. Rishi, Arun Iyer. Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2618.