Polyurethane Nanocapsules Research Articles

Tunable, reagent‐loaded polyurethane nanocapsules cleavable by NIR light

AbstractDual response polyurethane nanocapsules consisting of a hydrophilic core are synthesized via interfacial polyaddition of the diisocyanate monomers and different diols (VA‐060 and glycols) in inverse miniemulsion process. The presence of the water‐soluble NIR dye in the core and azo‐bonds in the polymer shell allows the selective release of encapsulated material triggered by temperature or NIR light. The capsules are characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The capsule degradation under external stimuli, like temperature and NIR light, is confirmed microscopically by TEM. Macroscopic evidence of the capsule cleavage was achieved by the incorporation of the chemical into the capsule core, and subsequent treatment of the capsules with NIR laser in the presence of the suitable reagent outside the capsules. A color‐forming chemical reaction occurred after the shell opening. The reactions were easily detected by visual observation of a color change and by UV–Vis spectroscopy.

Release of the model drug SR101 from polyurethane nanocapsules in porcine hair follicles triggered by LED-derived low dose UVA light

Hair follicles (HFs) are important drug delivery targets for the therapy of miscellaneous skin diseases and for skin antisepsis. Furthermore, HFs significantly contribute to drug delivery of topically applied substances. Nanoparticulate systems are excellently suited for follicular drug delivery as they entail the opportunity of directed drug transport into HFs. Moreover, they involve the possibility of an intrafollicular drug release initiated by extrinsic or intrinsic trigger mechanisms. In this study, we present a novel preclinical model for an anatomically and temporally targeted intrafollicular drug release. In vitro release kinetics of the model drug sulforhodamine 101 (SR101) from newly synthesized ultraviolet A (UVA)-responsive polyurethane nanocapsules (NCs) were investigated by fluorescence spectroscopy. Low power density UVA radiation provided by a UVA light emitting diode (LED) induced a drug release of over 50% after 2 min. We further utilized confocal laser scanning microscopy (CLSM) to investigate follicular penetration as well as intrafollicular drug release on an ex vivo porcine ear skin model. UVA-responsive degradation of the NCs at a mean follicular penetration depth of 509 ± 104 µm ensured liberation of SR101 in the right place and at the right time. Thus, for the first time a UVA-triggered drug release from NCs within HFs was demonstrated in the present study. Cytotoxicity tests revealed that NCs synthesized with isophorone diisocyanate show sufficient biocompatibility after UVA-induced cleavage. A considerable and controllable release of various water-soluble therapeutics could be reached by means of the presented system without risking any radiation-related tissue damage. Therefore, the implementation of the presented system into clinical routine, e.g. for preoperative antisepsis of HFs, appears very promising.

On-Demand and Long-Term Drug Delivery from Degradable Nanocapsules.

We have developed polyurethane nanocapsules as a platform for long-term delivery of drugs over weeks as well as on-demand delivery of drugs via ultrasound. We synthesized nanocapsules encapsulating either a model drug, fluorescein, or a clinically relevant drug, acriflavine, a HIF-1alpha inhibitor. Release studies demonstrated delivery of fluorescein or acriflavine over several weeks. Application of either an ultrasonic probe or a clinical grade, ultrasound imaging system used for assessing the retina led to release of a fraction of drug that could be tailored by the energy applied to the nanocapsules, and multiple pulses of release could be triggered over time with at least 10 separate release events triggered for each formulation. Being able to tailor the on-demand release over multiple cycles has the potential to fundamentally change how we can approach delivery of drugs for a variety of applications.

Preparation and Properties of Narrowly Dispersed Polyurethane Nanocapsules Containing Essential Oil via Phase Inversion Emulsification.

Narrowly dispersed polyurethane (PU) nanocapsules containing lavender essential oil (LO) were fabricated by polyaddition of toluene diisocyanate (TDI) trimer with polyol using a phase inversion emulsification technique. The particle size distribution (PSD), surface morphology, structure, encapsulation parameters, release properties, and thermal stability of nanocapsules have been characterized using a laser particle size analyzer (LPSA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectrum (FTIR), and thermogravimetric analysis (TGA), respectively. Experimental results demonstrate that the nanocapsules have a smaller size (ca. 268 nm), regular sphericity, uniform particle size (polydispersity index, PDI = 0.078), clear core-shell structure, and smooth surface. When the ratio of LO to TDI trimer is 5:10, the yield, encapsulation efficiency, and loading capacity of the nanocapsules can reach a maximum of 70.7%, 98.6%, and 64.8%, respectively. Furthermore, the release experiments showed that the cumulative release of LO from nanocapsules was only about 17% at room temperature and about 32% at 50 °C even after 20 days.

Mitochondria Targeting Non-Isocyanate-Based Polyurethane Nanocapsules for Enzyme-Triggered Drug Release.

Surface engineering of nanocarriers allows fine-tuning of their interactions with biological organisms, potentially forming the basis of devices for the monitoring of intracellular events or for intracellular drug delivery. In this context, biodegradable nanocarriers or nanocapsules capable of carrying bioactive molecules or drugs into the mitochondrial matrix could offer new capabilities in treating mitochondrial diseases. Nanocapsules with a polymeric backbone that undergoes programmed rupture in response to a specific chemical or enzymatic stimulus with subsequent release of the bioactive molecule or drug at mitochondria would be particularly attractive for this function. With this goal in mind, we have developed biologically benign nanocapsules using polyurethane-based, polymeric backbone that incorporates repetitive ester functionalities. The resulting nanocapsules are found to be highly stable and monodispersed in size. Importantly, a new non-isocyanate route is adapted for the synthesis of these non-isocyanate polyurethane nanocapsules (NIPU). The embedded ester linkages of these capsules' shells have facilitated complete degradation of the polymeric backbone in response to a stimulus provided by an esterase enzyme. Hydrophilic payloads like rhodamine or doxorubicin can be loaded inside these nanocarriers during their synthesis by an interfacial polymerization reaction. The postgrafting of the nanocapsules with phosphonium ion, a mitochondria-targeting receptor functionality, has helped us achieve the site-specific release of the drug. Co-localization experiments with commercial mitotracker green as well as mitotracker deep red confirmed localization of the cargo in mitochondria. Our in vitro studies confirm that specific release of doxorubicin within mitochondria causes higher cytotoxicity and cell death compared to free doxorubicin. Endogenous enzyme triggered nanocapsule rupture and release of the encapsulated dye is also demonstrated in a zebrafish model. The results of this proof-of-concept study illustrate that NIPU nanocarriers can provide a site-specific delivery vehicle and improve the therapeutic efficacy of a drug or be used to produce organelle-specific imaging studies.

Preparation and Characterization of Polyurethane Nanocapsules Containing Cassia alata Linn. Extract

Preparation and Characterization of Polyurethane Nanocapsules Containing Cassia alata Linn. Extract

Preparation and Photochromic Properties of Nanocapsules Containing Azo Compound with Polyurethane as Wall Material Using in Situ Polymerization

Photosensitive color-producing nanocapsules have been prepared with polyurethane as wall material via an in situ polymerization method. The polyurethane shell slowed down the colorization process for 12 s compared with azo compound in ethanol; however, the absorbance of azo compound increased by 29.7% in polyurethane nanocapsules. The absorbance of photoisomer decreased by 50% of the photostationary value during 60 s in polyurethane nanocapsules and 14 s in ethanol. The color depth of polyurethane nanocapsules was higher at the end of decolorization process. The half-life of azo compound and polyurethane nanocapsules were 135 min and 280 min, respectively.

Thermal properties of nanocapsules measured by scanning force microscopy methods

Heated micromechanical cantilevers were used to probe the thermal properties of nanogram samples in two ways: (i) as a micromechanical thermogravimetric balance and (ii) as a local nano-heater for heating individual objects. For micromechanical thermogravimetry, 6ng of polyurethane nanocapsules containing silverazide were freeze dried and attached to the micromechanical cantilever apex. The resonant frequency of the micromechanical cantilever upon heating was recorded. After heating to 250^oC, 25% mass was found remaining on the micromechanical cantilever. In order to image structural changes, the tip of the heatable micromechanical cantilever was positioned on individual nanocapsules weighing less than 6fg, and the capsule was imaged using a scanning force microscope. Then the cantilever was heated and temperature-deflection curves were recorded. Both methods revealed a decomposition temperature of 180^oC for silverazide encapsulated in a polyurethane nanocapsule. Topographic images of individual capsules after decomposition showed a rupture of the shell at one position.

Synthesis and characterization of triethylene glycol dimethacrylate nanocapsules used in a self-healing bonding resin

ObjectivesTo date, the production of highly durable dentine bonding is still a challenge. Self-healing bonding resins may provide a new direction for the improvement of the bonding durability. The objective of the current study was to synthesize polyurethane nanocapsules encapsulated with the core material triethylene glycol dimethacrylate (TEGDMA) for use as a major component in a self-healing bonding resin. MethodsTEGDMA nanocapsules were synthesized via interfacial polycondensation in a miniemulsion, and the TEGDMA nanocapsules were then characterized via Fourier-transform infrared (FTIR) spectrometer, field emission scanning electron microscopy (FESEM), and high-performance liquid chromatography (HPLC) to investigate the morphology, the average TEGDMA loading (DL%), and encapsulation efficiency (EE%). The mechanical property of dental adhesive with different concentrations (0, 3, 6, 9, and 12wt%) of the TEGDMA nanocapsules were also measured, and the cytotoxicity was investigated using an MTT assay. ResultsFTIR confirmed that the TEGDMA nanocapsules were successfully synthesized. These nanocapsules showed a high drug load. The bond strength of the dental adhesive incorporated with 9wt% TEGDMA nanocapsules was significantly higher compared with those of the other groups (P<0.001). Moreover, the biocompatibility of the dental adhesive was not affected by the incorporation of the TEGDMA nanocapsules. ConclusionsThe current study demonstrated the successful synthesis of TEGDMA nanocapsules, and the overall properties of the dental adhesive were not compromised.

Controlled Release from Polyurethane Nanocapsules via pH-, UV-Light- or Temperature-Induced Stimuli

Polyurethane nanocapsules consisting of an aqueous core and a polymeric shell with included azo bonds as obtained via interfacial polyaddition of the monomers toluene-2,4-diisocyanate (TDI) and an azo-containing containing diol (VA-060) in inverse miniemulsion allow the selective release of encapsulated material by stimuli such as temperature, UV light, or pH change. The capsule degradation was detected by measuring time-dependently the fluorescence intensities of the dye sulforhodamine SR101, which is dissolved as the fluorescent marker in the core, by exposing the capsules to the different stimuli. Furthermore, the capsules were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The main components during the capsules’ degradation were determined via nuclear magnetic resonance (NMR) spectrometry exemplary directly on the azo-monomer VA-060. The results present proof-of-principle studies of different controlled releases with a prototype of polyurethane capsules us...

Fluorescent Polyurethane Nanocapsules Prepared via Inverse Miniemulsion: Surface Functionalization for Use as Biocarriers

The functionalization of well-defined PU nanocapsules with an aqueous core prepared by performing a polyaddition at the interface of inverse (water-in-oil) miniemulsion droplets is demonstrated. The miniemulsion technique involving the nanoreactor concept allows one to obtain an encapsulation efficiency as high as 90% within the nanocapsules. A pH independent fluorescent dye is used as a model system for the aqueous core. By varying the molar ratio of the diol to the diisocyanate at a fixed surfactant concentration, the shell thickness of the nanocapsules can be finely tuned. The carboxy- and amino-functionalized surface of the nanocapsules can be tailored by an in-situ carboxymethylation reaction and by physical adsorption of a cationic polyelectrolyte, i.e. PAEMA or PEI. The increased uptake of amino-functionalized fluorescent nanocapsules by HeLa cells clearly demonstrates the potential of the functionalized nanocapsules to be successfully exploited as biocarriers.

Core–shell biocompatible polyurethane nanocapsules obtained by interfacial step polymerisation in miniemulsion

The goal of this paper was to present some original results obtained in the synthesis of oily core biocompatible polyurethane nanocapsules. We showed that the biocompatible oily core could play the major role of the costabilizer that prevents the Ostwald ripening in miniemulsion, by creating an osmotic pressure inside the droplets and counterbalancing the Laplace pressure. By the way, ibuprofen (a non-steroidal antalgic drug)-loaded nanocapsules were synthesised with Miglyol 812, a triglyceride oil currently used for drug delivery applications, as organic dispersed phase. The influence of various experimental parameters such as the sonifying conditions, the surfactant type, the concentration of ibuprofen on the size distribution were particularly examined. The chemical structure and microstructure of the nanocapsules were studied by 13C NMR and MALDI-TOF mass spectrometry. Finally, the core–shell morphology of the nanocapsules was investigated by electron microscopy experiments.

Polymeric Nanoreactors for Hydrophilic Reagents Synthesized by Interfacial Polycondensation on Miniemulsion Droplets

We describe a versatile method to obtain functional hollow nanoreactors with a hydrophilic liquid core. The synthesis of hollow polyurea, polythiourea, and polyurethane nanocapsules was performed by interfacial polycondensation or cross-linking reactions in inverse miniemulsion. The miniemulsions were built upon emulsification of a solution of amines or alcohols in a polar solvent with cyclohexane as the nonpolar continuous phase. The addition of suitable hydrophobic diisocyanate or diisothiocyanate monomers to the continuous phase allows the polycondensation or the cross-linking reactions to occur at the interface of the droplets. The wall thickness of the capsules can be directly tuned by the quantity of the reactants. The nature of the monomers and the continuous phase are the critical factors for the formation of the hollow capsules, which is explained by the interfacial properties of the system. The resulting polymer nanocapsules could be subsequently dispersed in water. The capsules were found to be...

Preparation of polyurethane nanocapsules by miniemulsion polyaddition

The encapsulation of organic liquids in polyurethane nanocapsules by interfacial miniemulsion polycondensation of isophorone diisocyanate and propanetriol has been performed. The influence of type and amount of encapsulated organic liquid has been studied and it was found that the encapsulation efficiency is dependent on the water solubility of the organic liquids, their interfacial tension against water and their compatibility with polyurethane. It was also shown how different types of surfactants and variations in pH and ionic strength of the continuous phase affected the stability during polymerization and the diameter of the miniemulsion droplets and the resulting nanocapsules. The long-chained anionic surfactant Disponil FES77 can be utilized over a larger pH range than SDS due to the contribution of steric stabilization. Relatively narrow size distributions were obtained.

Interfacial Polycondensation Encapsulation in Miniemulsion

Oily core polyurethane nanocapsules with a mean diameter of 200 nm were formulated in miniemulsion by interfacial polycondensation. The encapsulation process in miniemulsion was optimized by the choice of the surfactant type (anionic, cationic, or nonionic) and concentration; hexadecane was the costabilizer. Size distribution was studied by dynamic laser light scattering, and ζ potential was also determined. The size distribution appeared relatively narrow. Scanning and transmission electron microscopy experiments attested for the submicrometer size, the spherical shape of the capsules, and a smooth external wall. The thermal properties of the polyurethane wall were determined by DSC and TGA, with a fusion temperature around 40 °C, suggesting the presence of defaults in the macromolecular backbone such as irregular bounds of urethane and urea functions. The chemical structure of the polymer wall was studied by 13C NMR and MALDI−TOF mass spectrometry. Both methods attested for the presence of urethane and urea units in the macromolecular chain. MALDI−TOF experiments allowed the investigation of the microstructure of the polymer wall and proved the presence of urethane and urea homopolymer and urethane−urea copolymer. Although the determination of the molecular weight was not possible because of the high polydispersity of the sample, the mass range was comprised between 500 and 3000 Da, in accordance with the number-average molecular weight determined by size exclusion chromatography (PS standards).