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Psoriasis is a recurring, immune-mediated dermatological disorder. Many therapeutic agents are available for the treatment of psoriasis, including immunosuppressants and biologic ...treatments with immunosuppressant action. The employment of nanotechnology allows drug tailoring to achieve dermal targeting, improve efficacy and minimize undesirable effects. Here we discuss the use of the topical route in combination with nano-based drug delivery systems containing immunosuppressants for the management of psoriasis. This review is based on articles selected from 2011 to 2022, using the keywords “Psoriasis” AND “Immunosuppressants” AND “Nano*” in the main databases. Fifty-seven articles were retrieved, although only forty-two matched the inclusion criteria. Nanocarriers such as liposomes, ethosomes, niosomes, solid lipid nanoparticle, nanostructured lipid carriers and microspheres containing immunosuppressive drugs (methotrexate, cyclosporine, tacrolimus, and etanercept) were identified. The main findings of these studies are related to the improved in vitro/ex vivo permeation/penetration and therapeutic efficacy of nanoparticles in vitro and in vivo, compared to the drug in solution. Based on the studies discussed in this review, encapsulation in several types of nanocarriers decreases toxicity, dose, and dose frequency. Furthermore, it enables specific targeting of the active drug, pointing to the possibility of improving topical therapy for psoriasis. In conclusion, nanoformulations represent a novel and promising tool for psoriasis treatment.
Based on the structure of polymeric nanocapsules containing a lipid-dispersed core composed of caprylic/capric trygliceride (CCT) and sorbitan monostearate (SM), we hypothesized that varying the core ...component concentrations the drug release kinetic could be modulated. Our objective was also to determine the parameters which were responsible for controlling the drug release kinetics. The nanocapsules were prepared by interfacial deposition of poly(epsilon-caprolactone). Interfacial hydrolysis of indomethacin ester (IndOEt) was used to simulate a sink condition of release. Mathematical modeling showed that the IndOEt half-lives increased (198 to 378 and 263 to 508 min) with the increase in the core lipid concentrations, and that the release mechanism was the anomalous transport. By increasing the SM concentration, the diameters were constant (around 250 nm) and the surface areas increased (from 1.06 x 10(4) to 1.51 x 10(4) cm2 x ml(-1)), while by increasing the CCT concentration, the diameters increased (215 to 391 nm) and the surface areas reduced (1.46 x 10(4) to 1.06 x 10(4) cm2 x ml(-1)). The presence of SM increased the viscosity of CCT and the IndOEt apparent permeability decreased from 4.26 x 10(-7) to 2.54 x 10(-7) cm x s(-1), while for CCT series, the apparent permeability was constant around 3.0 x 10(-7) cm x s(-1). A mathematical correlation was established and the IndOEt apparent permeability can be estimated by the SM concentration. In conclusion, varying the CCT and SM concentrations the IndOEt release was controlled by the nanocapsule surface area and by the viscosity of the core, respectively.
This review is based on selected reports from 2004 to 2014 and provides a comprehensive and updated overview of the state of the art related to the drug delivery advantages of polymeric nanocapsules, ...which are a specific type of polymeric nanoparticles used for improvement of biological effects. Special attention is given to the application of nanocapsules to increase the chemical and photostability of drugs, to modulate the interaction with cells and tissues, to reduce adverse effects of drugs, and to increase the drug efficiency and/or bioavailability. Moreover, this review covers in vitro and in vivo studies, highlighting interesting examples of drugs from several therapeutic classes for which efficacy is improved by encapsulation in different types of nanocapsules, especially in lipid‐core nanocapsules. We also briefly present the first results obtained so far attesting to the safety of using polymeric nanocapsules for drug delivery. WIREs Nanomed Nanobiotechnol 2015, 7:623–639. doi: 10.1002/wnan.1334
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
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Treatment of bacterial airway infections is essential for cystic fibrosis therapy. However, effectiveness of antibacterial treatment is limited as bacteria inside the mucus are ...protected from antibiotics and immune response. To overcome this biological barrier, ciprofloxacin was loaded into lipid-core nanocapsules (LNC) for high mucus permeability, sustained release and antibacterial activity. Ciprofloxacin-loaded LNC with a mean size of 180nm showed a by 50% increased drug permeation through mucus. In bacterial growth assays, the drug in the LNC had similar minimum inhibitory concentrations as the free drug in P. aeruginosa and S. aureus. Interestingly, formation of biofilm-like aggregates, which were observed for S. aureus treated with free ciprofloxacin, was avoided by exposure to LNC.
With the combined advantages over the non-encapsulated drug, ciprofloxacin-loaded LNC represent a promising drug delivery system with the prospect of an improved antibiotic therapy in cystic fibrosis.
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The human papillomavirus (HPV) infection, which is strongly related to cervical cancer, can be reduced by the topical application of imiquimod. Some strategies have been used to ...increase the adhesion and penetration of drugs through the vaginal mucosa. Two of them are the development of mucoadhesive semisolid formulations and the development of polymeric nanocarriers. In this paper, we hypothesize that the combined use of these two strategies results in a better performance of the formulation to retain imiquimod into the vaginal tissue. Aiming this, two different systems are proposed: (a) chitosan-coated poly(ε-caprolactone)-nanocapsules incorporated into hydroxyethylcellulose gel (HEC-NCimiq-chit), and (b) poly(ε-caprolactone)-nanocapsules incorporated into chitosan hydrogel (CHIT-NCimiq). These formulations were submitted to three main tests: mucoadhesivity by interaction, permeation and washability test (or retention test). We developed an integrative index that allows comparing the global performance of the proposed formulations by considering jointly the results of these three tests. Thus, when considered the integrative indexes for the formulations, our results show that CHIT-NCimiq presents the best performance for the treatment of HPV.
Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main ...capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution CH-ET-CP) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% CH-ET-CP and 23% commercial product) and severe (8% CH-ET-CP and 69% commercial product) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation.
Several studies have reported that orally ingested trans-resveratrol is extensively metabolized in the enterocyte before it enters the blood and target organs. Additionally, trans-resveratrol is ...photosensitive, easily oxidized and presents unfavorable pharmacokinetics. Therefore, it is of great interest to stabilize trans-resveratrol in order to preserve its biological activities and to improve its bioavailability in the brain. Here, trans-resveratrol was loaded into lipid-core nanocapsules and analyzed for particle size, polydispersity and zeta potential. The nanocapsule distribution in brain tissue was evaluated by intraperitoneal (i.p.) and gavage routes in healthy rats. The lipid-core nanocapsules had a mean diameter of 241 nm, a polydispersity index of 0.2, and a zeta potential of -15 mV. No physical changes were observed after 1, 2 and 3 months of storage at 25 degrees C. Lipid-core nanocapsules showed high entrapment of trans-resveratrol and displayed a higher trans-resveratrol concentration in the brain, the liver and the kidney after daily i.p. or gavage administration than that observed for the free trans-resveratrol. Because trans-resveratrol is a potent cyclooxygenase-1 inhibitor, gastrointestinal damage was evaluated. The animals that were administered with trans-resveratrol-loaded lipid-core nanocapsules showed significantly less damage when compared to those administered with free trans-resveratrol. In summary, lipid-core nanocapsules exhibited great trans-resveratrol encapsulation efficiency. trans-Resveratrol-loaded lipid-core nanocapsules increased the concentration of trans-resveratrol in the brain tissue. Gastrointestinal safety was improved when compared with free trans-resveratrol. Thus, trans-resveratrol-loaded lipid-core nanocapsules may be used as an alternative potential therapeutic for several diseases including Alzheimer's disease.
The hemocompatibility of nanoparticles is of critical importance for their systemic administration as drug delivery systems. Formulations of lipid-core nanocapsules, stabilized with polysorbate ...80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D4,3: 129 and 134nm), dynamic light scattering (119nm and 133nm), nanoparticle tracking (D50: 124 and 139nm) and particle mobility (zeta potential: −15.1mV and +9.3mV) analysis. In vitro hemocompatibility studies were carried out with mixtures of nanocapsule suspensions in human blood at 2% and 10% (v/v). The prothrombin time showed no significant change independently of the nanocapsule surface potential or its concentration in plasma. Regarding the activated partial thromboplastin time, both suspensions at 2% (v/v) in plasma did not influence the clotting time. Even though suspensions at 10% (v/v) in plasma decreased the clotting times (p<0.05), the values were within the normal range. The ability of plasma to activate the coagulation system was maintained after the addition of the formulations. Suspensions at 2% (v/v) in blood showed no significant hemolysis or platelet aggregation. In conclusion, the lipid-core nanocapsules uncoated or coated with chitosan are hemocompatible representing a potential innovative nanotechnological formulation for intravenous administration.
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•LNC are surrounded by micellar structures.•Spherical-cylindrical transformation of micellar structures at the hydrophilic corona of the LNC.•Chitosan-coated LNC: growth inhibition of ...clinical isolates, multidrug-resistant Staphylococcus aureus and Aspergillus ssp.
Lecithin-polysorbate 80-lipid-core nanocapsules (LNC) or chitosan-coated LNC (LNC-CS) containing or not dapsone (DAP) were prepared and characterized. Particle size varied from 126 to 130nm (laser diffraction) and from 114 to 125nm (z-average diameter by dynamic light scattering). The pH values ranged from 4.15 to 4.57 and zeta potential inverted from −15 (LNC) to +23mV (LNC-CS) and from −13 (DAP-LNC) to +21mV (DAP-LNC-CS). Transmission electron microscopy analysis evidenced four layers of micellar structures coating LNC, constituting a hydrophilic corona. For the first time, a sequence of spherical to cylindrical micellar transformation was observed at the nanocapsule corona. Biological assays demonstrated that DAP-LNC, LNC-CS and DAP-LNC-CS act as growth inhibitors of five clinical isolates of Staphylococcus aureus, which exhibited multidrug-resistance to ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin and penicillin G, and six strains of three filamentous fungi species: Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. The nanoencapsulation of dapsone improved the inhibitory activity of the drug in both assays. In addition, the presence of chitosan in the formulations provided a better performance of the formulation in the case of S. aureus, while the influence of the nanoencapsulated drug was more pronounced in the antifungal activity.
Alzheimer’s disease (AD), a neurodegenerative disorder exhibiting a gradual decline in cognitive function, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and ...amyloid-β (Aβ) peptide. Available drugs for AD therapy have small effect sizes and do not alter disease progression. Several studies have been shown that resveratrol is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we compared the neuroprotective effects of free resveratrol treatment with those of resveratrol-loaded lipid-core nanocapsule treatment against intracerebroventricular injection of Aβ1-42 in rats. Animals received a single intracerebroventricular injection of Aβ1-42 (2 nmol), and 1 day after Aβ infusion, they were administered either free resveratrol (RSV) or resveratrol-loaded lipid-core nanocapsules (5 mg/kg, each 12 h, intraperitoneally), for 14 days. Aβ1-42-infused animals showed a significant impairment on learning memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels. Furthermore, animals exhibited activated astrocytes and microglial cells, as well as disturbance in c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β) activation, beyond destabilization of β-catenin levels. Our results clearly show that by using lipid-core nanocapsules, resveratrol was able to rescue the deleterious effects of Aβ1-42 while treatment with RSV presented only partial beneficial effects. These findings might be explained by the robust increase of resveratrol concentration in the brain tissue achieved by lipid-core nanocapsules. Our data not only confirm the potential of resveratrol in treating AD but also offer an effective way to improve the efficiency of resveratrol through the use of nanodrug delivery systems.
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