Biocompatible Nanocapsules Research Articles

Interfacial Engineering of Biocompatible Nanocapsules for Near-Infrared-Triggered Drug Release and Photothermal Therapy.

Chemotherapy is an effective option for cancer treatment. However, its clinical application is often limited by the severe side effects of chemical drugs. To overcome these limitations, a novel drug-loaded phase-change nanocapsule system is developed. These nanocapsules are assembled via one-step electrostatic self-assemblythrough guided interfacial engineering. The phase change material core nanocapsules demonstrate great photothermal-controlled drug release performance and exhibit excellent tumor-targeting drug delivery performance both in vitro and in vivo via the binding of hyaluronic acid shell on the nanocapsule surface with corresponding receptors on the tumor cell membrane. The phototherapy function of the nanocapsules enhances immune activation within the tumor microenvironment, as demonstrated by flow cytometry and multiplex immunohistochemistry. The developed nanocapsules are biocompatible, versatile, and scalable and offer a promising smart delivery platform for controllable near-infrared triggered drug release and photothermal therapy.

Biocompatible Nanocapsules for Self-Healing Dental Resins and Bone Cements.

Bone cements and dental resins are methacrylate-based materials that have been in use for many years, but their failure rates are quite high with essentially all dental resins failing within 10 years and 25% of all prosthetic implants will undergo aseptic loosening. There are significant healthcare costs and impacts on quality of life of patients. Self-healing bone cements and resins could improve the lifespan of these systems, reduce costs, and improve patient outcomes, but they have been limited by efficacy and toxicity of the components. To address these issues, we developed a self-healing system based on a dual nanocapsule system. Two nanocapsules were synthesized, one containing an initiator and one encapsulating a monomer, both in polyurethane shells. The monomer used was triethylene glycol dimethacrylate. The initiator capsules synthesized contained benzoyl peroxide and butylated hydroxytoluene. Resins containing the nanocapsules were tested in tension until failure, and the fractured surfaces were placed together. 33% of the samples showed self-healing behaviors to the point where they could be reloaded and tested in tension. Furthermore, the capsules and their components showed good biocompatibility with Caco-2 cells, a human epithelial cell line suggesting that they would be well tolerated in vivo.

Copolyelectrolyte-Based Nanocapsules for Oral Monoclonal Antibody Therapy: A Mesoscale Modeling Survey.

Antibody therapy generally requires parenteral injection to attain the required bioavailability and pharmacokinetics, but improved formulations may slow enzymatic degradation of the antibody in the gastrointestinal tract, permitting the use of noninvasive oral delivery. Rationally designed carrier materials can potentially improve therapeutic activity both by shielding fragile biopharmaceuticals from proteolytic degradation and targeting specific receptors in vivo. One potentially useful class of protein carriers is block copolyelectrolytes, one polyelectrolyte plus one neutral hydrophilic polymer block, that self-assemble into stable micelles, providing a simple and biocompatible nanocapsule separating the protein from the outer medium. Here, we develop and implement an integrated mesoscale model to design molecular structures for block copolyelectrolyte nanocapsules predicted to protect Trastuzumab, an antibody used to treat breast cancer, in the low pH gastrointestinal tract and to selectively release this antibody in the more neutral intestinal environment. The simulations show a tightly packed self-assembled core-shell structure at pH = 3 that is ruptured and dynamically reassembled into a weaker structure at pH = 7. Our model identifies that the designed block copolyelectrolyte characteristics, such as block length ratio, can control the level of drug protection and release in vivo, providing simple design rules for engineering polyelectrolyte-based formulations that may allow oral administration of targeted antibody chemotherapies.

Investigation of Inertial Cavitation of Sonosensitive and Biocompatible Nanoparticles in Flow - Through Tissue- Mimicking Phantoms Employing Focused Ultrasound

Abstract A promising approach to drug delivery applications for chemotherapeutics is the use of drug carriers to reduce the total amount of cytostatics, minimizing side effects. In addition, the carriers, loaded with the drug, can be guided to the tumorous tissue via the vascular system, which enables a local drug release (LDR). In our case, LDR is activated due to the sonosensitive behavior of the nanocapsules by inertial cavitation (IC) caused by focused ultrasound (FUS). Thereby, IC is excited by employing sound pressures within the recommended limit allowed for diagnostic ultrasound. In order to verify this drug delivery approach for its clinical suitability, a tissue-mimicking flow -through phantom, containing a small vessel, is used. Investigations have shown that the drug releasing cavitation effect associated with the sonosensitive and biocompatible nanocapsules also occurs in fine vessel structures, even in the case of moving particles and vessel diameters dc smaller than the wavelength λ.

A Smart Theranostic Nanocapsule for Spatiotemporally Programmable Photo-Gene Therapy.

The therapeutic performance of DNAzyme-involved gene silencing is significantly constrained by inefficient conditional activation and insufficient cofactor supply. Herein, a self-sufficient therapeutic nanosystem was realized through the delicate design of DNAzyme prodrugs and MnO2 into a biocompatible nanocapsule with tumor-specific recognition/activation features. The indocyanine green (ICG)-modified DNA prodrugs are designed by splitting the DNAzyme and then reconstituted into the exquisite catalyzed hairpin assembly (CHA) amplification circuit. Based on the photothermal activation of ICG, the nanocapsule was disassembled to expose the MnO2 ingredient which was immediately decomposed into Mn2+ ions to supplement an indispensable DNAzyme cofactor on-demand with a concomitant O2 generation for enhancing the auxiliary phototherapy. The endogenous microRNA catalyzes the amplified assembly of DNA prodrugs via an exquisite CHA principle, leading to the DNAzyme-mediated simultaneous silencing of two key tumor-involved mRNAs. This self-activated theranostic nanocapsule could substantially expand the toolbox for accurate diagnosis and programmable therapeutics.

A Smart Theranostic Nanocapsule for Spatiotemporally Programmable Photo‐Gene Therapy

AbstractThe therapeutic performance of DNAzyme‐involved gene silencing is significantly constrained by inefficient conditional activation and insufficient cofactor supply. Herein, a self‐sufficient therapeutic nanosystem was realized through the delicate design of DNAzyme prodrugs and MnO2 into a biocompatible nanocapsule with tumor‐specific recognition/activation features. The indocyanine green (ICG)‐modified DNA prodrugs are designed by splitting the DNAzyme and then reconstituted into the exquisite catalyzed hairpin assembly (CHA) amplification circuit. Based on the photothermal activation of ICG, the nanocapsule was disassembled to expose the MnO2 ingredient which was immediately decomposed into Mn2+ ions to supplement an indispensable DNAzyme cofactor on‐demand with a concomitant O2 generation for enhancing the auxiliary phototherapy. The endogenous microRNA catalyzes the amplified assembly of DNA prodrugs via an exquisite CHA principle, leading to the DNAzyme‐mediated simultaneous silencing of two key tumor‐involved mRNAs. This self‐activated theranostic nanocapsule could substantially expand the toolbox for accurate diagnosis and programmable therapeutics.

Tamoxifen-loaded PLA/DPPE-PEG lipid-polymeric nanocapsules for inhibiting the growth of estrogen-positive human breast cancer cells through cell cycle arrest

The strategy of drug encapsulation with biocompatible polymeric nanocapsules could be a promising approach to improve the delivery of poorly water-soluble drugs for cancer therapy. The aim of this study was to investigate the drug delivery of tamoxifen from biocompatible nanocapsules made of poly(D,L-lactide) (PLA) core and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DPPE-PEG) shell in the treatment of breast cancer. The analytical techniques such as FTIR, XRD, SEM, and TEM were used to investigate the structure of nanocapsules. Tamoxifen drug encapsulation efficiency and loading percentages as well as release kinetics at different pH values and temperatures were used to confirm the appropriate performance of these novel nanocapsules. The maximum tamoxifen release occurred at 40 °C, pH = 4. Based on the SEM and TEM images, the sizes of nanocapsules were between 57 and 159 nm. In order to investigate the anticancer effects and cytotoxicity of encapsulated tamoxifen in PLA/DPPE-PEG nanocapsules, the tetrazolium-based colorimetric (MTT) assay and cell cycle arrest analysis on MCF-7 breast cancer cell were performed. Also, cell cycle–related gene expressions of p53 and p21 in treated MCF-7 cells with tamoxifen-loaded PLA/DPPE-PEG nanocapsules were evaluated. The results of MTT cell proliferation experiments exhibited an increase in the cytotoxicity of tamoxifen nanocapsules on MCF-7 cell line compared with free tamoxifen. The 1.2-fold increase in the G1 stage compared with the control group in the cell cycle arrest protocol as well as the notable overexpression of p53 and p21 genes suggested that these nanocapsules arrested cell cycle in MCF-7 cells.

Synthesis of nano-capsules via aqueous emulsion RCMP-PISA and encapsulation

Synthesis of nano-capsules using aqueous RCMP-PISA and encapsulation of rhodamine-B (Rh-B).

Steric hindrance boosted upconversion for low-power imaging in vivo

Upconversion based on triplet-triplet annihilation (TTA-UC) has received much attention due to its unique ability to effectively harvest low-energy photons in the solar spectrum for widespread investigations involving energy, environment, and bioapplication. However, the utilization of conventional TTA-UC systems for low-power bioimaging in vivo is still a challenge due to their incompatibility and moderate efficiency in aqueous media. Herein, we pioneer the molecular modification strategy by introducing steric hindrance to the BODIPY annihilators to realize robust TTA-UC in biocompatible nanocapsule. The improved molecules could maintain excellent luminescence even at a very high concentration wherein the separation distance between neighbouring chromophores was reduced to facilitate the pivotal process of Dexter energy transfer. In this way, the encapsulated TTA-UC system became highly efficient in biological circumstance with quantum efficiency ФUC of 6.3%. Consequently, the constructed nanocapsule was capable of operating at low-power with high contrast for in vivo imaging.

Intracellular Delivery of an Antibody Targeting Gasdermin-B Reduces HER2 Breast Cancer Aggressiveness.

Gasdermin B (GSDMB) overexpression/amplification occurs in about 60% of HER2 breast cancers, where it promotes cell migration, resistance to anti-HER2 therapies, and poor clinical outcome. Thus, we tackle GSDMB cytoplasmic overexpression as a new therapeutic target in HER2 breast cancers. We have developed a new targeted nanomedicine based on hyaluronic acid-biocompatible nanocapsules, which allow the intracellular delivery of a specific anti-GSDMB antibody into HER2 breast cancer cells both in vitro and in vivo. Using different models of HER2 breast cancer cells, we show that anti-GSDMB antibody loaded to nanocapsules has significant and specific effects on GSDMB-overexpressing cancer cells' behavior in ways such as (i) lowering the in vitro cell migration induced by GSDMB; (ii) enhancing the sensitivity to trastuzumab; (iii) reducing tumor growth by increasing apoptotic rate in orthotopic breast cancer xenografts; and (iv) diminishing lung metastasis in MDA-MB-231-HER2 cells in vivo. Moreover, at a mechanistic level, we have shown that AbGB increases GSDMB binding to sulfatides and consequently decreases migratory cell behavior and may upregulate the potential intrinsic procell death activity of GSDMB. Our findings portray the first evidence of the effectiveness and specificity of an antibody-based nanomedicine that targets an intracellular oncoprotein. We have proved that intracellular-delivered anti-GSDMB reduces diverse protumor GSDMB functions (migration, metastasis, and resistance to therapy) in an efficient and specific way, thus providing a new targeted therapeutic strategy in aggressive HER2 cancers with poor prognosis.

Multi-reactive surfactant and miniemulsion Atom Transfer Radical Polymerization: An elegant controlled one-step way to obtain dextran-covered nanocapsules

A convenient one-step method is developed to prepare potentially biocompatible nanocapsules (NCs) with a biocompatible oily core (Miglyol 810, M810), a poly(methyl methacrylate) (PMMA) shell and a dextran coverage. For that, a multi-reactive dextran derivative containing both hydrophobic phenoxy and ATRP initiator groups is used as inisurf (macroinitiator and stabilizer) in an Activator Generated by Electron Transfer-Atom Transfer Radical Polymerization (AGET-ATRP) miniemulsion process. Such dextran inisurfs are shown to efficiently stabilize the direct miniemulsion of MMA with M810 as co-stabilizer, and to confine the polymerization at the oil/water interface via their multiple initiator sites. Grafted copolymers are produced from the inisurf, whose grafts constitute the inner polymeric shell of NCs and are linked to the dextran coverage. The confinement of such polymerization at interface is found to reduce initiator group efficiency, but also to improve both polymerization kinetics and control in comparison with one molecular model initiator. Increasing M810 content promotes the oily core/PMMA shell phase separation during polymerization and the formation of slightly larger NCs, without affecting polymerization kinetics.

Synthesis and characterization of novel biocompatible nanocapsules encapsulated lily fragrance

Fragranced products are wildly used in our daily life. However, their storage, application and quality are severely influenced by their strong volatility. In order to overcome these natural defects of fragrances, fragrance encapsulation approaches have been developed recently. In this study, a mild, simple and low-cost method of fragrance encapsulation was invented. Liposomes composed of soya lecithin/DSPE-PEG2000/PLGA were prepared to encapsulate lily fragrance (LF). And these nanosized fragrance products was named LF-NPs. The hydrodynamic diameters of LF-NPs were approximately 100 nm and their encapsulation efficiency was up to 21.9%. Besides, LF-NPs could also prolong the release time of lily fragrance. Finally, the cytotoxicity tests indicated that LF-NPs offered biocompatibility. Therefore, LF-NPs were expected to have application prospects.

Vault Nanoparticles: Chemical Modifications for Imaging and Enhanced Delivery.

Vault nanoparticles represent promising vehicles for drug and probe delivery. Innately found within human cells, vaults are stable, biocompatible nanocapsules possessing an internal volume that can encapsulate hundreds to thousands of molecules. They can also be targeted. Unlike most nanoparticles, vaults are nonimmunogenic and monodispersed and can be rapidly produced in insect cells. Efforts to create vaults with modified properties have been, to date, almost entirely limited to recombinant bioengineering approaches. Here we report a systematic chemical study of covalent vault modifications, directed at tuning vault properties for research and clinical applications, such as imaging, targeted delivery, and enhanced cellular uptake. As supra-macromolecular structures, vaults contain thousands of derivatizable amino acid side chains. This study is focused on establishing the comparative selectivity and efficiency of chemically modifying vault lysine and cysteine residues, using Michael additions, nucleophilic substitutions, and disulfide exchange reactions. We also report a strategy that converts the more abundant vault lysine residues to readily functionalizable thiol terminated side chains through treatment with 2-iminothiolane (Traut's reagent). These studies provide a method to doubly modify vaults with cell penetrating peptides and imaging agents, allowing for in vitro studies on their enhanced uptake into cells.

Upconversion luminescence tracking of gene delivery via multifunctional nanocapsules

The real-time fluorescence tracking of gene delivery is very important as it helps to figure out how a vector enters a cell and also to follow its fate within the cell interior. Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great potential in biomedical applications in virtue of their unique optical and biological properties. Herein, we report a simple and versatile strategy to fabricate a multifunctional nanocapsule for effective gene delivery and real-time luminescence tracking. The hydrophobic UCNPs were modified by positively charged amphiphilic polymer together with polyethylene glycol-poly(lactic-co-glycolic acid) (PEG–PLGA) polymer, affording biocompatible nanocapsules with high gene loading capacity and good stability. Red UC luminescence of UCNPs are able to track the delivery of nanocapsules in cells without background fluorescence interference, in the meantime, the green fluorescence of green fluorescence protein (GFP) expressed by the pDNA could subtly monitor the gene transfection efficacy. The results demonstrated that our nanocapsule has ideal biocompatibility, satisfactory gene loading capacity and great bioimaging ability, which is promising for imaging guided cell therapy and gene engineering.

Interfacial click chemistry for improving both dextran shell density and stability of biocompatible nanocapsules

Dextran-covered nanocapsules (NCs) have been obtained by emulsion-evaporation method coupled with an in situ click Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction occurring at liquid/liquid interface. To assure biocompatibility and biodegradability of NCs, α-alkyne PLA was chosen as inner shell and Miglyol 810 (M810) as oily core. NCs were covered by a hydrophilic superficial layer of dextran modified by azide-terminated 6-carbon aliphatic side chains, so-called DexN3. DexN3 was dissolved in the aqueous phase, but during emulsion process it migrated at the interface to act both as stabilizer and as reactant. Click reaction occurred at the oil-in-water interface between azide functions from DexN3 and alkyne groups of PLA present in the organic phase. Influence of different parameters, such as catalyst system or sonication conditions, has been studied on CuAAC reaction efficiency. CuSO4/AAsc was proven to be the most efficient catalyst. NCs characteristics in terms of particle size distribution, dextran coverage, colloidal stability in presence of salt and of SDS (competitive surfactant) as well as their morphology have been investigated. Core–shell NCs were obtained with various M810 content. Covalent linkages between PLA shell and dextran coverage improved colloidal stability of NCs, even in presence of SDS but also increased dextran density and thickness, in comparison to non-clicked NCs.

Novel biocompatible nanocapsules for slow release of fragrances on the human skin

There is a growing demand for fragranced products, but due to the poor aqueous solubility and instability of fragrance molecules, their use is limited. Nowadays, fragrance encapsulation in biocompatible nanocontainer material is emerging as a novel strategy to overcome the evaporation of volatile molecules and to prolong the sensory characteristics of fragrance molecules and the longevity of perfumes. The objective of this study was to develop an innovative sustained release system of perfume, by entrapping fragrance molecules in a polymeric nanocarrier; the impact of this strategy on the human axillary microbiome was further assessed. Stabilised poly-l-lactic acid nanocapsules (PLA-NCs) with a diameter of approximately 115 nm were prepared through nanoprecipitation. Size and morphology of the capsules were evaluated using Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). Two model hydrophobic compounds, chlorobenzene and fluorescein, representing two different types of functionalised molecules, were encapsulated in PLA-NCs with an efficiency rate of 50%. Different release behaviours were seen, dependent on hydrophobicity. For hydrophobic compounds, a steady release was observed over 48hours. The polymeric nanocarriers did not impact the human axillary microbiome. Because of the slow and sustained release of fragrances, encapsulation of molecules in biocompatible NCs can represent a revolutionary contribution to the future of toiletries, body deodorant products, and in washing and cleaning sectors.

Biomaterial properties evaluation of poly(vinyl acetate-alt-maleic anhydride)/chitosan nanocapsules

Nanocapsules with diameter around 100 nm based on a natural polymer (chitosan) and a synthetic polymer poly(vinyl acetate-alt-maleic anhydride) [poly(MAVA)] by interfacial condensation method were prepared. The present study proposes a new type of biocompatible nanocapsules based on poly(vinyl acetate-alt-maleic anhydride-chitosan) (MCS) able to become a reliable support for inclusion and release of drugs. The spherical shape of the nanocapsules was evidenced by scanning electron microscopy. Nanocapsules presented a good Norfloxacin loading and release capacity. Haemocompatibility tests have demonstrated that the nanocapsules present a low toxicity and a good compatibility with sanguine medium. The biocompatibility properties of the nanocapsules after their intraperitoneal administration in rats were evidenced by histopathological examination of different organs (brain, liver, kidney, and lung). The results are encouraging and the nanocapsules can be used as controlled drug delivery systems.

Gemcitabine-Loaded Biocompatible Nanocapsules for The Effective Treatment of Human Cancer

To encapsulate the nucleoside gemcitabine (GEM) in novel PEGylated polymeric nanocapsules (NanoGEM). The biological activity of NanoGEM was tested both in vitro and in vivo in comparison with the free drug. The NanoGEM was made of polylactic acid and allowed the entrapment of a great amount of GEM. The NanoGEM showed mean sizes of approximately 200 nm, a polydispersity index of approximately 0.1 and a ζ-potential of -30 mV. It exerted a stronger, quicker effect on the reduction of HEK293 cell growth in vitro in comparison with free GEM and had an in vivo antitumoral effect on the proliferation of xenograft tumors at a drug dosage tenfold less than its saline solution. The employment of nanocapsules increased the plasmatic half-life of the drug and allowed a great accumulation of GEM inside the tumors. NanoGEM represents a promising new tool for the treatment of cancer.

Preparation of biocompatible nanocapsules with temperature-responsive and bioreducible properties

Stimuli-responsive biocompatible nanocarriers are very promising for controlled drug release. Here, we report redox- and temperature-responsive biocompatible nanocapsules prepared by growing a temperature-responsive biocompatible shell from 3-(trimethoxysilyl)propyl methacrylate-modified silica nanoparticles (SiO2-MPS) viaprecipitation polymerization, cross-linking the shell with bioreducible chemical linkages, and subsequently removing the silica core by hydrofluoric acid etching. The produced nanocapsules are redox- and temperature-responsive. TEM, FT-IR, TGA, and XPS were used to characterize the nanocapsules. Dynamic light scattering (DLS) was performed to demonstrate the bioreducible and temperature-responsive properties of the nanocapsules. The lower critical solution temperature (LCST) of the nanocapsules can be tuned precisely. Fluorescein isothiocyanate (FITC) was encapsulated into the nanocapsules and used as a model drug molecule to demonstrate the controlled release behavior under external stimuli.

Formation of Biocompatible Nanocapsules with Emulsion Core and Pegylated Shell by Polyelectrolyte Multilayer Adsorption

The aim of this work was to develop a novel method of preparation of loaded nanosize capsules based on liquid core encapsulation by biocompatible polyelectrolyte (PE) multilayer adsorption, with or without pegylated outermost layer. Using AOT (docusate sodium salt) as emulsifier, we obtained cores, stabilized by an AOT/PLL (poly-L-lysine hydrobromide) surface complex. These positively charged cores were encapsulated by layer-by-layer adsorption of polyelectrolytes, biocompatible polyanion PGA (poly-L-glutamic acid sodium salt), and biocompatible polycation PLL. We used the saturation method for formation of consecutive layers, and we determined the optimal conditions concerning concentration of surfactant and polyelectrolytes to form stable shells. The average size of the obtained capsules was 60 nm. Pegylated external layer were prepared using PGA-g-PEG (PGA grafted by PEG poly(ethylene glycol)). The capsules were stable for at least a period of 3 months. These nanocapsules were biocompatible when tested for cytotoxicity in a cellular coculture assay and demonstrated no or very low nonspecific binding to peripheral blood mononuclear cells when tested by flow cytometry. In order to study drug effects on leukemia cells, beta-carotene and vitamin A have been encapsulated as model drugs.