Model Hydrophobic Drug Research Articles

Nanosized carriers based on amphiphilic poly-N-vinyl-2-pyrrolidone for intranuclear drug delivery.

Ability to deliver drugs into the cell nuclei can significantly increase the efficacy of cancer therapies, in particular in the case of multidrug-resistant cancer Results: Polymer nanocarriers based on amphiphilic thiooctadecyl-terminated poly-N-vinyl-2-pyrrolidone were produced and loaded with a model hydrophobic drug,curcumin. Two commonly used loading approaches - emulsification and ultrasonic dispersion - were found to lead to two different size distributions with distinctively different biological effect. While nanocarriers produced via the emulsion method penetrated cells by dynamin-dependent endocytic mechanisms, sub-100 nm dispersion-produced nanocarriers were capable of crossing the membranes via biologically independent mechanisms. This finding opens an intriguing possibility of intranuclear delivery by merely tailoring the size of polymeric carriers, thus promising a new approach for cancer therapies.

Development of Novel Biodegradable Enrofloxacin–Silica Composite for In Vitro Drug Release Kinetic Studies

A sustained drug delivery system is developed by using nonionic polymer to formulate drug release rate from silica capsules. To serve this purpose, silica capsules filled with poly(ethylene glycol) (PEG) were incorporated with a veterinary antibiotic drug enrofloxacin (ENF); as a model hydrophobic drug by using a general and facile sol–gel route. The physicochemical properties of the prepared drug-loaded composites were investigated by scanning electron microscope (SEM), nitrogen adsorption, Fourier transform infrared spectroscopy and thermal analysis (TGA). The impact of the media’s ionic strength on the drug release was evaluated over a range of 0–0.4 M to simulate the gastrointestinal feed in two physiological pH conditions. Sodium chloride was applied for ionic concentration adjustment due to its ability to salt out polymers in the midrange of the lyotropic series. Simultaneously, the drug release kinetics was evaluated by fitting experimental data to common empirical (zero-order, first order and Higuchi) and semi-empirical (Ritger–Peppas and Sahlin–Peppas) models. The drug release kinetics from capsules revealed a non-Fickian diffusion and pure relaxation-controlled release. Of these models, Sahlin–Peppas equation best fit the release data of ENF. To determine the best model, non-linear regressions were carried out.

Preparation of poly(butylene succinate)‐poly[2‐(dimethylamino)ethyl methacrylate] copolymers and their applications as carriers for drug delivery

AbstractCopolymers of poly[2‐(dimethylamino)ethyl methacrylate]–poly(butylene succinate)–poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA–PBS–PDMAEMA, PDBD) were synthesized through a chain‐extension reaction. The thermal properties characterized using differential scanning calorimetry showed that the introduction of PDMAEMA chains slightly decreased the melting temperature of PBS. The water contact angle of PDBD copolymer films with media of various pH decreased with a decrease of pH. This should be ascribed to the conformational transition of PDMAEMA blocks from a compact coil to an expanding shape in accordance with the variation of the pH of the surroundings. The results of dynamic light scattering and scanning electron microscopy revealed that PDBD copolymers could form spherical micelles with small particle size and narrow particle size distribution. Furthermore, drug loading (loading content, ca 10%; encapsulation efficiency, ca 60%) and release experiments were conducted using doxorubicin as a hydrophobic model drug. The results of release experiments of copolymer nanomicelles showed that these micelles had pH‐responsive properties. © 2018 Society of Chemical Industry

Tween 20‐Assisted Synthesis of Uniform Mesoporous Silica Nanospheres with Wormhole Porosity for Efficient Intracellular Curcumin Delivery

AbstractWe report a green and straightforward protocol to prepare uniform mesoporous silica nanospheres (MSNs) as well as core/shell‐like spherical particles by utilizing small amounts of Tween 20, a biocompatible and biodegradable surfactant. Due to small amount of surfactant employed in the synthesis, these MSNs can be easily purified and readily dispersed in water. TEM analysis showed presence of wormhole‐like framework‐confined mesoporosity along with high surface area (upto 250 m2/g) in these MSNs. Size‐tunability of these nanospheres was achieved by simple variation of the ethanol:water ratio during the synthesis. Powder X‐ray diffraction (XRD) and low angle XRD, respectively, showed amorphous nature and similar pore ordering for all the samples prepared using this protocol. These MSNs showed effective, post‐synthetic uptake of model hydrophobic drug curcumin to yield stable aqueous dispersions. High biocompatibility and ready internalization by mammalian cells mainly through clathrin‐independent, caveolae‐ and lipid raft‐mediated endocytosis was observed for these MSNs. Efficient intracellular delivery of curcumin using these MSNs was achieved in MDA‐MB‐231 (Breast cancer) cells. Thus, this work offers facile protocol for synthesis of uniform and biocompatible MSNs with promising drug delivery capabilities.

Albumin-covered lipid nanocapsules exhibit enhanced uptake performance by breast-tumor cells

Liquid lipid nanocapsules (LLN) represent a promising new generation of drug-delivery systems. They can carry hydrophobic drugs in their oily core, but the composition and structure of the surrounding protective shell determine their capacity to survive in the circulatory system and to achieve their goal: penetrate tumor cells. Here, we present a study of LLN covered by the protein human serum albumin (HSA) and loaded with curcumin as a hydrophobic model drug. A cross-linking procedure was performed to further strengthen the protective protein layer. Physicochemical properties and release kinetics of the nanocapsules were investigated, and cellular uptake and killing capacity were evaluated on the human breast-cancer line MCF-7. The nanocapsules exhibited a half maximal inhibitory concentration (IC50) capacity similar to that of free curcumin, but avoiding problems associated with excipients, and displayed an outstanding uptake performance, entering cells massively in less than 1 min.

Synthesis of temperature, pH, light and dual-redox quintuple-stimuli-responsive shell-crosslinked polymeric nanoparticles for controlled release

Herein, we prepared a novel quintuple-stimuli-responsive shell-crosslinked (SCL) nanocontainer in respond to temperature, pH, light, and oxidation or reduction species. The well-defined amphiphilic diblock copolymer poly(2-methacryloyloxyethyl ferrocenecarboxylate)-(5-propargylether-2-nitrobenzyl bromoisobutyrate)-poly(dimethylaminoethyl methacrylate) (PMAEFc-ONB-PDMAEMA) was synthesized via atom transfer radical polymerization (ATRP) and click chemistry. The diblock copolymer self-assembled into spherical micelles with a uniform size in aqueous media as non-crosslinked (NCL) micelles, and then the micelles were crosslinked by N,N′-bis(bromoacetyl) cystamine (BBAC) through quaternization reaction between the nitrogen of DMAEMA and the bromine of BBAC to receive the SCL micelles which shrunk at higher temperature, swelled at acidic pH or a low concentration of hydrogen peroxide (H2O2), decrosslinked by a small amount of DL-dithiothreitol (DTT), and were disrupted with DTT and UV light. The multi-stimuli-sensitive properties of the SCL micelles were characterized in detail by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence spectra, and UV–Vis spectra. Owing to the protective effect of the crosslinked network, light response behaviors of the NCL and SCL micelles were different. In contrast to the single stimulus, the combined stimuli could trigger and regulate the release of hydrophobic drug model more effectively and precisely from the SCL micelles. The obtained multi-stimuli-responsive nanocontainers may lead to a new generation of controlled release in the fields of nanotechnology and biotechnology.

Feasibility of Using Gluconolactone, Trehalose and Hydroxy-Propyl Gamma Cyclodextrin to Enhance Bendroflumethiazide Dissolution Using Lyophilisation and Physical Mixing Techniques.

Purpose: Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug. Methods: In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Results: The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min. Conclusions: the physical mixing and freeze drying processes significantly increased the percentage of drug release with time.

Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle: in vitro and in vivo evaluation

Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40 mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400 mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications.

Fabrication of cationic nanostructures from short self-assembling amphiphilic mixed α/β-pentapeptide: Potential candidates for drug delivery, gene delivery, and antimicrobial applications

The present article describes designing and fabrication of nanostructures from a mixed α/β-pentapeptide, Lys-βAla-βAla-Lys-βAla, which majorly contains non-natural β-alanine residues in the backbone with two α-lysine residues at 1- and 4-positions. The amphiphilic pentapeptide showed the ability to self-assemble into cationic nanovesicles in an aqueous solution. The average size of peptide nanostructures was found to be ~270 nm with a very high cationic charge of ~+40 mV. TEM micrographs revealed the average size of the same nanostructures ~80 nm bearing vesicular morphology. CD and FTIR spectroscopic studies on self-assembled pentapeptide hinted at random coil conformation which was also correlated with conformational search program using Hyper Chem 8.0. The pentapeptide nanostructures were then tested for encapsulation of hydrophobic model drug moieties, L-Dopa, and curcumin. Transfection efficiency of the generated cationic nanostructures was evaluated on HEK293 cells and compared the results with those obtained in the presence of chloroquine. The cytotoxicity assay performed using MTT depicted ~75–80% cell viability. The obtained nanostructures also gave positive results against both Gram-negative and Gram-positive bacterial strains. Altogether the results advocate the promising potential of the pentapeptide foldamer, H-Lys-βAla-βAla-Lys-βAla-OEt, for drug and gene delivery applications along with the antimicrobial activity.

Engineered Cellular Uptake and Controlled Drug Delivery Using Two Dimensional Nanoparticle and Polymer for Cancer Treatment.

Two major problems in chemotherapy, poor bioavailability of hydrophobic anticancer drug and its adverse side effects causing nausea, are taken into account by developing a sustained drug release vehicle along with enhanced bioavailability using two-dimensional layered double hydroxides (LDHs) with appropriate surface charge and its subsequent embedment in polymer matrix. A model hydrophobic anticancer drug, raloxifene hydrochloride (RH), is intercalated into a series of zinc iron LDHs with varying anion charge densities using an ion exchange technique. To achieve significant sustained delivery, drug-intercalated LDH is embedded in poly(ε-caprolactone) (PCL) matrix to develop intravenous administration and to improve the therapeutic index of the drug. The cause of sustained release is visualized from the strong interaction between LDH and drug, as measured through spectroscopic techniques, like X-ray photoelectron spectroscopy, infrared, UV-visible spectroscopy, and thermal measurement (depression of melting temperature and considerable reduction in heat of fusion), using differential scanning calorimeter, followed by delayed diffusion of drug from polymer matrix. Interestingly, polymer nanohybrid exhibits long-term and excellent in vitro antitumor efficacy as opposed to pure drug or drug-intercalated LDH or only drug embedded PCL (conventional drug delivery vehicle) as evident from cell viability and cell adhesion experiments prompting a model depicting greater killing efficiency (cellular uptake) of the delivery vehicle (polymer nanohybrid) controlled by its better cell adhesion as noticed through cellular uptake after tagging of fluorescence rhodamine B separately to drug and LDH. In vivo studies also confirm the sustained release of drug in the bloodstream of albino rats using polymer nanohybrid (novel drug delivery vehicle) along with a healthy liver vis-à-vis burst release using pure drug/drug-intercalated LDHs with considerable damaged liver.

Hydrogels based on poly(methyl vinyl ether-co-maleic acid) and Tween 85 for sustained delivery of hydrophobic drugs

Hydrogels based on poly(methyl vinyl ether-co-maleic acid) and Tween 85 were prepared for hydrophobic drug delivery. The hydrogels were synthesized following a simple procedure carried out in solid state. The process did not require the use of any solvent and, as it is based on an esterification reaction, no toxic by-products were obtained. The resulting hydrogels contained Tween 85 inside the structure and due to the amphiphilic nature of this compound, hydrophobic domains within the hydrogel structure were formed. The obtained hydrogels showed good swelling capacities ranging from 100% to 600%. The esterification reaction that took place between poly(methyl vinyl ether-co-maleic acid) and Tween 85 was confirmed by infrared spectroscopy. Hydrogels were loaded with a hydrophobic drug model, Curcumin (CUR), showing that the hydrogels were able to retain up to 36 mg of CUR per g of hydrogel. Additionally, the synthesized hydrogels provided in vitro sustained CUR release over periods of up to 30 days. Finally, and due to the mucoadhesive nature of the prepared materials, one of the hydrogels was tested in vitro as an oral drug delivery system. For this purpose, the selected material was milled into microparticles (45–90 µm diameter). The release of CUR from the microparticles was evaluated under simulated gastric and intestinal conditions. The microparticles were able to release their cargos in 7 h. However, further work is required to optimize this system for oral drug delivery applications.

Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) statistical copolymers and a series of three poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-polystyrene (PND-b-PS-C12) diblock polymers were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization, in which the molecular weight of the thermoresponsive PND corona block was held constant while the polystyrene core block length was varied. The corona thickness and density of the micelles in phosphate-buffered saline (PBS, pH = 6.5) were quantified by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Two hydrophobic model drugs, phenytoin and nilutamide, were used to examine the drug–polymer interactions in aqueous solution. Intermolecular interactions between the diblock polymer micelle corona and both drugs were revealed by 2D 1H nuclear Overhauser effect spectroscopy (NOESY). The drug–polymer “binding” strength, quantified by diffusion ordered NMR spectroscopy (DOSY)...

Microspherical Particles of Solid Dispersion of Polyvinylpyrrolidone K29-32 for Inhalation Administration.

Inhalation administration is a promising alternative to the invasive drug delivery methods. The particle size required for ideal drug aerosol preparation is between 1 and 3 μm. The application of microspherical particles of solid dispersions enhances bioavailability of poorly soluble drugs due to the solubilization. In the present work, the spray drying process of the production of microspherical particles of solid dispersions of polyvinylpyrrolidone K29-32 with model hydrophobic drug, phenacetin, was optimized using the results of DSC, PXRD, and viscometry. The diameter of the obtained particles is within 1–3 μm range. The Gibbs energy of dissolution in water was shown to be negative for the mixture with polymer/phenacetin mass ratio 5 : 1. We have demonstrated that the optimal size distribution for the inhalation administration is obtained for microspherical particles produced using spray caps with 7.0 μm hole size. The dissolution rates of phenacetin from the produced microspherical particles were faster than that of drug powder. As evidenced by powder X-ray diffraction data, phenacetin stayed in amorphous state for 4 months in microspherical particles of solid dispersions. According to the obtained results, strategic application of the spray drying process could be beneficial for the improvement of the pharmaceutical properties of model drug, phenacetin.

Preparation and Characterization of Simvastatin Nanocapsules: Encapsulation of Hydrophobic Drugs in Calcium Alginate.

During past few years, development of methods for physical encapsulation of drugs in biocompatible materials in mild conditions for poorly water-soluble hydrophobic drugs which are sensitive to hydrolytic conditions is of high interest in biomedical and pharmaceutical industries. The encapsulation can improve the drug solubility while decreases its side effects besides controlling its pharmacokinetic profile which results in the overall improvement of the therapeutic efficacy. In the current paper, we provide a detailed protocol for encapsulation of poorly water-soluble hydrophobic drugs which is a development of the previously developed protocol of nanocapsule formation by complex formation on the interface of emulsion droplets. The newly developed protocol is based on nanocapsule formation by complex formation on the interface of emulsion droplets except using no organic solvent for potential targeted drug delivery to glioblastoma cells. Simvastatin as a model of hydrophobic drugs of high hydrolytic sensitivity was encapsulated in calcium alginate hydrogel as a biocompatible matrix using the developed protocol. Simvastatin belongs to a group of mevalonate cascade inhibitors (statins) which have recently been considered as a possible new approach in cancer treatment especially glioblastoma. As a cholesterol biosynthesis inhibitor, it is very important to deliver statins only to target cells and not intact cells using targeted drug delivery strategies to avoid dysregulation of cholesterol biosynthesis in normal tissue. To prepare the statin drug nanocarrier's, the drug was first dissolved in polysorbate 20 nonionic surfactant solution, and then peptide modified calcium alginate was deposited on the micelles interface at neutral pH and 30°C. The prepared nanocapsules were spherical in shape and very small in size (i.e., 17±5nm). The drug content of the nanocapsules was 117.3mgg-1 and the drug loading efficiency for a 5-mg initial amount of the drug was 23.5%±3.1%.

Phenytoin-Bovine Serum Albumin interactions - modeling plasma protein – drug binding: A multi-spectroscopy and in silico-based correlation

The study focused on the analysis of the nature and site of binding of Phenytoin (PHT) -(a model hydrophobic drug) with Bovine Serum Albumin (BSA) (a model protein used as a surrogate for HSA). Interactions with defined amounts of Phenytoin and BSA demonstrated a blue shift (hypsochromic -change in the microenvironment of the tryptophan residue with decrease in the polar environment and more of hydrophobicity) with respect to the albumin protein and a red shift (bathochromic -hydrophobicity and polarity related changes) in the case of the model hydrophobic drug. This shift, albeit lower in magnitude, has been substantiated by a fairly convincing, Phenytoin-mediated quenching of the endogenous fluorophore in BSA. Spectral shifts studied at varying pH, temperatures and incubation periods (at varying concentrations of PHT with a defined/constant BSA concentration) showed no significant differences (data not shown). FTIR analysis provided evidence of the interaction of PHT with BSA with a stretching vibration of 1737.86cm−1, apart from the vibrations characteristically associated with the amine and carboxyl groups respectively. Our in vitro findings were extended to molecular docking of BSA with PHT (with the different ionized forms of the drug) and the subsequent LIGPLOT-based analysis. In general, a preponderance of hydrophobic interactions was observed. These hydrophobic interactions corroborate the tryptophan-based spectral shifts and the fluorescence quenching data. These results substantiates our hitherto unreported in vitro/in silico experimental flow and provides a basis for screening other hydrophobic drugs in its class.

PLMA-b-POEGMA Amphiphilic Block Copolymers as Nanocarriers for the Encapsulation of Magnetic Nanoparticles and Indomethacin.

We report here on the utilization of poly(lauryl methacrylate)-b-poly(oligo ethylene glycol methacrylate) (PLMA-b-POEGMA) amphiphilic block copolymers, which form compound micelles in aqueous solutions, as nanocarriers for the encapsulation of either magnetic iron oxide nanoparticles or iron oxide nanoparticles, and the model hydrophobic drug indomethacin in the their hydrophobic core. The mixed nanostructures were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM) in terms of their structure and solution properties. Magnetophoresis experiments showed that the mixed solutions maintain the magnetic properties of the initial iron oxide nanoparticles. Results indicate that the cumulative hydrophilic/hydrophobic balance of all components determines the colloidal stability of the nanosystems. The effect of salt and bovine serum albumin (BSA) protein concentration on the structure of the mixed nanostructures was also investigated. Disintegration of the mixed nanostructures was observed in both cases, showing the importance of these parameters in the structure formation and stability of such complex mixed nanosystems.

Temperature controlled loading and release of curcumin in polyelectrolyte multilayers thin films

The temperature triggered loading and release of hydrophobic model drug (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) (curcumin) from polyelectrolyte multilayer (PEM) thin films was demonstrated. Thin films built from the layer-by-layer (LbL) deposition of poly(diallyldimethylammonium chloride) (PDADMAC) and poly(4-styrene sulfonate) (PSS) were dipped in curcumin and studied as patches that could be used in temperature controlled drug delivery applications. Three different solvents (methanol, ethanol and isopropanol) were mixed with different fractions of water (from 60:40% to 95:5% aqueous:organic solvent) and fixed amount of curcumin (100 ppm). The loading of curcumin in the PEM increased when the polarity of the solvent mixture was increased or when the temperature was decreased. Interestingly, curcumin could spontaneously be released in warm water and as an example, curcumin was loaded PEM film at 5 °C and release at 37 °C thus demonstrating the body temperature triggered release of a hydrophobic model drug. Using this method a new type of transdermal patch for the release of hydrophobic drugs from PEM membrane would be possible.

Formation of Polymeric Nanocubes by Self-Assembly and Crystallization of Dithiolane-Containing Triblock Copolymers.

Template-free fabrication of non-spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self-assembly from aqueous solutions at room temperature. Nanocubes with edges of 40-200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks. These polymers self-assemble into 28±5 nm micelles in water. Upon drying, micelle aggregation and a kinetically controlled crystallization of central blocks evidently induce solid cubic particle formation. An approach for preserving the structures of these cubes in water by thiol- or photo-induced crosslinking was developed. The ability to solubilize a model hydrophobic drug, curcumin, was also explored.

Formation of Polymeric Nanocubes by Self‐Assembly and Crystallization of Dithiolane‐Containing Triblock Copolymers

AbstractTemplate‐free fabrication of non‐spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self‐assembly from aqueous solutions at room temperature. Nanocubes with edges of 40–200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks. These polymers self‐assemble into 28±5 nm micelles in water. Upon drying, micelle aggregation and a kinetically controlled crystallization of central blocks evidently induce solid cubic particle formation. An approach for preserving the structures of these cubes in water by thiol‐ or photo‐induced crosslinking was developed. The ability to solubilize a model hydrophobic drug, curcumin, was also explored.

Curcumin loaded nanocarriers obtained by self-assembly of a linear d,l-octapeptide-poly(ethylene glycol) conjugate

The preparation and characterization of a novel linear d,l-octapeptide-poly(ethylene glycol) conjugate, formulated as biocompatible nanocarrier of hydrophobic drugs, was reported. The PEGylated d,l-octapeptide was designed to self-assemble in core-shell nanoparticles with rod-like morphology obtained by exploiting the self-assembling properties of linear peptides with regularly alternating enantiomeric sequences in tubular structures. The conformational properties of the conjugate and its self-assembling capability were assessed through dynamic light scattering, energy filtered-transmission electron microscopy, scanning electron microscopy, circular dichroism, fluorescence, and proton nuclear magnetic resonance spectroscopy. Furthermore, the upload in peptide-polymer nanoparticles of curcumin, adopted as model of hydrophobic drugs, was performed. In fact, despite accumulating evidence suggests that curcumin has different therapeutic activities, its use in medicine is limited to the very low water solubility, low bioavailability and chemical instability. This work addresses such drawbacks showing that nanoparticles obtained by For-(d-Phe-l-Cys(Acm))4-NH-(CH2-CH2-O)45-CH3 self-assembly are effective carriers for curcumin with high drug loading and sustained drug release.