Search Results (39)

Polymeric vesicles, characterized by enhanced colloidal stability, excellent mechanical properties, controllable surface functionality, and adjustable membrane thickness, are extremely useful in nano- and bio-technology for potential applications as nanosized carriers for drugs and enzymes. However, a few preparative steps are necessary to achieve a unilamellar vesicle with a narrow size distribution. Herein, we report the spontaneous formation of unilamellar polymeric vesicles with nanometer sizes (<50 nm), fabricated by simply mixing diblock copolymers (P(EO-AGE)(2K-2K) and P(EO-AGE)(0.75K-2K)) with differing hydrophilic mass fractions in aqueous solutions. Depending on the mixing ratio of block copolymers and the temperature, the block copolymer mixtures self-assemble into various nanostructures, such as spherical and cylindrical micelles, or vesicles. The self-assembled structures of the block copolymer mixtures were characterized by small-angle neutron scattering, resulting in a phase diagram drawn as a function of temperature and the mixing condition. Notably, the critical temperature for the micelle-to-vesicle phase transition can be easily controlled by altering the mixing conditions; it decreases with an increase in the concentration of one of the block copolymers. Full article

Novel amphiphilic block copolymers of N-vinyl pyrrolidone (NVP) and either n-hexyl methacrylate (HMA, PNVP-b-PHMA) or stearyl methacrylate (SMA, PNVP-b-PSMA) were prepared by RAFT polymerization techniques and the sequential addition of monomers starting from the polymerization of NVP and using two different Chain Transfer Agents, CTAs. PNVP-b-PHMA are amorphous block copolymers containing constituent blocks with both high and low Tg values, whereas PNVP-b-PSMA are amorphous–semi-crystalline copolymers. Samples with different molecular weights and compositions were obtained. The copolymers were microphase-separated, but partial mixing was also observed. The presence of the amorphous PNVP block reduced the crystallinity of the PSMA blocks in the PNVP-b-PSMA copolymers. The thermal stability of the blocks was influenced by both constituents. The self-assembly behavior in THF, which is a selective solvent for polymethacrylate blocks, and in aqueous solutions, where PNVP was soluble, was examined. Unimolecular or low-aggregation-number micelles were obtained in THF for both types of samples. On the contrary, high-aggregation-number, spherical, and compact micelles were revealed in aqueous solutions. The increase in the steric hindrance of the side ester group of the polymethacrylate chain led to slightly lower degrees of association. The hydrophobic compound curcumin was efficiently encapsulated within the micellar core of the supramolecular structures in aqueous solutions. Micelles with higher aggregation numbers were more efficient in the encapsulation of curcumin. The results of this study were compared with those obtained from other block copolymers based on PNVP. Full article

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA₃₅-b-PCL₇₀-b-PDMAEMA₃₅) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO₁₀₀-b-PPO₆₅-b-PEO₁₀₀) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production). Full article

We introduce a novel concept in nucleic acid delivery based on the use of mixed polymeric micelles (MPMs) as platforms for the preparation of micelleplexes with DNA. MPMs were prepared by the co-assembly of a cationic copolymer, poly(1-(4-methylpiperazin-1-yl)-propenone)-b-poly(d,l-lactide), and nonionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) block copolymers. We hypothesize that by introducing nonionic entities incorporated into the mixed co-assembled structures, the mode and strength of DNA binding and DNA accessibility and release could be modulated. The systems were characterized in terms of size, surface potential, buffering capacity, and binding ability to investigate the influence of composition, in particular, the poly(ethylene oxide) chain length on the properties and structure of the MPMs. Endo–lysosomal conditions were simulated to follow the changes in fundamental parameters and behavior of the micelleplexes. The results were interpreted as reflecting the specific structure and composition of the corona and localization of DNA in the corona, predetermined by the poly(ethylene oxide) chain length. A favorable effect of the introduction of the nonionic block copolymer component in the MPMs and micelleplexes thereof was the enhancement of biocompatibility. The slight reduction of the transfection efficiency of the MPM-based micelleplexes compared to that of the single-component polymer micelles was attributed to the premature release of DNA from the MPM-based micelleplexes in the endo–lysosomal compartments. Full article

Background/Objectives: Nintedanib (NTD), a triple tyrosine kinase receptor inhibitor, is the recommended first-line tackling option for idiopathic pulmonary fibrosis (IPF). Nevertheless, the adequacy of NTD is curtailed by issues associated with its low solubility, first-pass effect, poor bioavailability, and liver toxicity. The objective of our work was to develop a non-invasive intratracheal (i.t.) nanoparadigm based on NTD-loaded polymeric mixed micelles (NTD-PMMs) that can effectively treat IPF by sustaining the release of NTD, and snowballing its bioavailability, solubility, and efficacy. Methods: Design-Expert^® software was used to optimize various NTD-PMMs formulations via Box–Behnken design adopting the thin-film hydration technique. The optimum formulation was chosen and in vivo tested in a rat model to explore its comparative bioavailability and toxicity. Results: The formulation composition with 309.217 mg of Soluplus, 150 mg of Tween 80, and 40 mg of sodium deoxycholate was found to fulfill the requisites of an optimum NTD-PMMs formulation. The optimum NTD-PMMs formulation divulged 90.26% entrapment efficiency with a surface charge of −14.72 mV and a nanoscale diameter of 61.36 nm. Also, it substantially sustained the release of NTD by 66.84% after 24 h and manifested a pronounced stability. In vivo histopathology investigations verified the safety of NTD-PMMs delivered intratracheally. Moreover, pharmacokinetic analyses disclosed accentuated relative bioavailability of the optimized NTD-PMMs by 2.4- and 3.82-fold as compared with both the i.t. and oral crude NTD suspensions, respectively. Conclusions: Overall, the current results elicited the potential of PMMs to serve as a promising pulmonary nanovector for the targeted delivery of NTD. Full article

The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels. Full article

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug. Full article

This study was designed to formulate a polymeric mixed micelle (PMM) formulation to sustainably release fexofenadine (FEX) to treat allergic conjunctivitis effectively. A 3² factorial design was employed where the studied factors were PL90G amount (X₁) and Pluronic (F127 and P123) mixture ratio (X₂), and the dependent variables were entrapment efficacy (EE, Y₁, %), particle size (PS, Y₂, nm), zeta potential (ZP, Y₃, mV), and the percent of drug released after 6 h (Q6h, Y₄, %). The optimized formula was blended with a hydrogel base to develop an FEX-PMM hydrogel, where the safety and efficiency of this hydrogel were evaluated using in vivo studies. The EE% of FEX-PMM ranged from 62.15 ± 2.75 to 90.25 ± 1.48%, the PS from 291.35 ± 6.43 to 467.95 ± 3.60 nm, the ZP from −5.41 ± 0.12 to −9.23 ± 0.23 mV, and the Q6h from 50.27 ± 1.11 to 95.38 ± 0.92%. The Draize test results confirmed the safety of the FEX-PMM hydrogel. Furthermore, the FEX-PMM hydrogel showed rapid recovery in animals with induced allergic conjunctivitis compared to the free drug hydrogel. These results assure PMM’s capability to deliver FEX to the conjunctival surface in a sustained pattern, consequently achieving better therapeutic outcomes. Full article

The anionic polymer sodium alginate, a linear copolymer of guluronic and mannuronic acids, is primarily present in brown algae. Copolymers are used in the sodium alginate preparation process to confer on the material strength and flexibility. Micelles and other polymeric nanoparticles are frequently made using the triblock copolymer Pluronic^® F-127. The purpose of the present study is to determine the effect of sodium alginate’s viscosity (low and medium) and the presence of Pluronic^® F-127 micelles on the swelling behavior of the prepared pure beads and those loaded with Pluronic^® F-127 micelles. The Pluronic^® F-127 nanomicelles have a size of 120 nm. The swelling studies were carried out at pH = 1.2 (simulated gastric fluid-SGF) for two hours and at pH = 6.8 (simulated intestinal fluid-SIF) for four more hours. The swelling of both low- and medium-viscosity alginate beads was minor at pH = 1.2, irrespective of the use of Pluronic^® F-127 nanomicelles. At pH = 6.8, without Pluronic^® F-127, the beads showed an enhanced swelling ratio for the first four hours, which was even higher in the medium-viscosity alginate beads. With the addition of Pluronic^® F-127, the beads were dissolved in the first and second hour, in the case of the low- and medium-alginate’s viscosity, respectively. In other words, the behavior of the mixed hydrogels was the same during the swelling experiments. Therefore, the presence of Pluronic^® F-127 nanomicelles and medium-viscosity sodium alginate leads to a higher swelling ratio. A model drug, acetyl salicylic acid (ASA), was also encapsulated in the mixed beads and ASA’s release studies were performed. In conclusion, the prepared systems, which are well characterized, show potential as delivery platforms for the oral delivery of active pharmaceutical ingredients and biopharmaceuticals. Full article

Block copolymers synthesized via Atom Transfer Radical Polymerization from alkyl acrylate and t-butyl acrylate and the subsequent hydrolysis of the t-butyl acrylate to acrylic acid were systematically varied with respect to their hydrophobic part by the variation in the alkyl chain length and the degree of polymerisation in this block. Depending on the architecture of the hydrophobic part, they had a more or less pronounced tendency to form copolymer micelles in an aqueous solution. They were employed for the preparation of IPECs by mixing the copolymer aggregates with the polycations polydiallyldimethylammonium chloride (PDADMAC) or q-chit. The IPEC structure as a function of the composition was investigated by Static Light and Small Angle Neutron Scattering. For weakly-associated block copolymers (short alkyl chain), complexation with polycation led to the formation of globular complexes, while already existing micelles (long alkyl chain) grew further in mass. In general, aggregates became larger upon the addition of further polycation, but this growth was much more pronounced for PDADMAC compared to q-chit, thereby leading to the formation of clusters of aggregates. Accordingly, the structure of such IPECs with a hydrophobic block depended largely on the type of complexing polyelectrolyte, which allowed for controlling the structural organisation via the molecular architecture of the two oppositely charged polyelectrolytes. Full article

In this work, mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA₂₉-b-PCL₇₀-b-PDMAEMA₂₉) and a non-ionic poly(ethylene oxide)–b-poly(propylene oxide)–b-poly(ethylene oxide) (PEO₉₉-b-PPO₆₇-b-PEO₉₉) triblock copolymers, blended at different molar ratios, were developed. The key physicochemical parameters of MPMs, including size, size distribution, and critical micellar concentration (CMC), were evaluated. The resulting MPMs are nanoscopic with a hydrodynamic diameter of around 35 nm, and the ζ-potential and CMC values strongly depend on the MPM’s composition. Ciprofloxacin (CF) was solubilized by the micelles via hydrophobic interaction with the micellar core and electrostatic interaction between the polycationic blocks, and the drug localized it, to some extent, in the micellar corona. The effect of a polymer-to-drug mass ratio on the drug-loading content (DLC) and encapsulation efficiency (EE) of MPMs was assessed. MPMs prepared at a polymer-to-drug mass ratio of 10:1 exhibited very high EE and a prolonged release profile. All micellar systems demonstrated their capability to detach pre-formed Gram-positive and Gram-negative bacterial biofilms and significantly reduced their biomass. The metabolic activity of the biofilm was strongly suppressed by the CF-loaded MPMs indicating the successful drug delivery and release. The cytotoxicity of empty and CF-loaded MPMs was evaluated. The test reveals composition-dependent cell viability without cell destruction or morphological signs of cell death. Full article

Orally administered antipsychotic drugs are the first-line treatment for psychotic disorders, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions jeopardize clinical outcomes, resulting in patient non-compliance. The design formulation strategies for enhancing brain drug delivery has been a major challenge, mainly due to the restrictive properties of the blood–brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed the advantage of the intranasal route when compared to oral and intravenous administration, as it allows direct nose-to-brain drug transport via neuronal pathways, reducing systemic side effects and maximizing therapeutic outcomes. In addition, the incorporation of antipsychotic drugs into nanosystems such as polymeric nanoparticles, polymeric mixed micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes and spanlastics, has proven to be quite promising. The developed nanosystems, having a small and homogeneous particle size (ideal for nose-to-brain delivery), high encapsulation efficiency and good stability, resulted in improved brain bioavailability and therapeutic-like effects in animal models. Hence, although it is essential to continue research in this field, the intranasal delivery of nanosystems for the treatment of schizophrenia, bipolar disorder and other related disorders has proven to be quite promising, opening a path for future therapies with higher efficacy. Full article

This research concerns the investigation of the preparation of polymeric nanocarriers containing a flavonoid—naringenin, xanthohumol or isoxanthohumol—based on Pluronics by the thin-film formation method. The size of the formed micelles and their stability upon dilution were evaluated using Dynamic light scattering (DLS) analysis; the high values of the drug loading and the encapsulation efficiency confirmed that the proposed systems of flavonoids delivery consisting of Pluronic P123 and F127 nanomicelles could effectively distribute the drug into tumour tissues, which makes these nanocarriers ideal candidates for passive targeting of cancer cells by the enhanced permeation and retention (EPR) effect. The in vitro cytotoxicity of proposed flavonoids in the Pluronic formulations was investigated by the SRB assay with human colon cancer cells. We designed mixed polymeric micelles, which was a successful drug delivery system for the case of naringenin not being able to enhance the bioavailability and cytotoxic activity of xanthohumol and isoxanthohumol. Furthermore, it was observed that the higher amount of polymer in the formulation achieved better cytotoxic activity. Full article

Orally administered antipsychotic drugs are the first line of treatment in the management of psychotic disorders that affect millions of people globally and have a tremendous impact on patient and family lives, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions hinder clinical outcomes, resulting in patient non-compliance. The design and implementation of adequate formulation strategies for enhancing drug delivery and targeting to the brain has been a significant challenge, mainly due to the restrictive properties of the blood–brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed that there is evidence of the advantage of the intranasal route when compared to oral and intravenous administration, as it allows the possibility of direct nose-to-brain transport via neuronal olfactory and trigeminal pathways, reducing systemic side effects, and maximizing therapeutic outcomes. In addition, the formulation of polymeric and solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes, Spanlastics and polymeric mixed micelles is a promising approach since they have a reduced particle size, ideal for nose-to-brain delivery, stability, high encapsulation efficiency, enhanced drug solubility, and drug protection from enzymatic degradation. Nevertheless, it is essential to continue research in this field, conducting more long-term studies with greater uniformity so that the true potential of these formulations can be assessed and a transposition into the pharmaceutical industry is someday possible. Full article

The present study is focused on the development of cannabidiol-loaded polymeric nanomicelles as a drug delivery system with neuroprotective effects. Cannabidiol was loaded in Pluronic micelles (Pluronic P123 or its combination with Pluronic F127) possessing an average diameter smaller than 50 nm and high encapsulation efficiency for the hydrophobic drug (80% and 84%, respectively). The successful encapsulation and transformation of cannabidiol in amorphous phase were observed by IR spectroscopy and X-ray diffraction, respectively. Studies with neuroblastoma cells (SH-SY5Y and Neuro-2a) showed that the pure cannabidiol caused a dose-dependent reduction of cell viability, whereas its loading into the micelles decreased cytotoxicity. Further, neuroprotective effects of pure and micellar cannabidiol were examined in a model of H₂O₂-induced oxidative stress in both neuroblastoma cells. The pre-treatment of cell lines with cannabidiol loaded into the mixed Pluronic P123/F127 micelles exerted significantly stronger protection against the oxidative stress compared to pure cannabidiol and cannabidiol in single Pluronic P123 micelles. Interestingly, the empty mixed P123/F127 micelles demonstrated protective activity against the oxidative stress. In conclusion, the study revealed the opportunity to formulate a new drug delivery system of cannabidiol, in particular nanosized micellar aqueous dispersion, that could be considered as a perspective platform for cannabidiol application in neurodegenerative diseases. Full article