Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Is imiquimod a promising drug to treat oral mucosa diseases? A scoping review and new perspectives.

Imiquimod (IMQ) is a chemotherapeutic and immunostimulant drug that is applied topically, demonstrating antitumor and antiviral activities. The objective of this review was to compile data on the off-label use of IMQ in oral mucosal diseases. IMQ has exhibited effectiveness in the treatment of various oral mucosal conditions, including oral carcinogenic lesions, neoplasms, HPV-related lesions and autoimmune disorders. Although IMQ holds promise as a potential strategy for addressing oral mucosal lesions, it is important to note that significant side effects have been frequently reported. Nonetheless, it is crucial to develop and test new technological systems, such as the combination of nanotechnology with innovative drug delivery platforms. These advancements aim to minimize side effects and prolong the drug's contact time with the mucosa, preventing its removal by salivary flow.

Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Development of Annexin A1-surface-functionalized metal-complex multi-wall lipid core nanocapsules and effectiveness on experimental colitis.

Annexin A1 (AnxA1), a 37KDa protein, is secreted by inflammatory and epithelial cells and displays anti-inflammatory and wound healing activities in intestinal bowel diseases. Herein, we aimed to functionalize recombinant AnxA1 (AnxA1) on multi-wall lipid core nanocapsules (MLNC) and investigate its effectiveness on experimental colitis. MLNC were prepared by covering lipid core nanocapsules (LNC) with chitosan, which coordinates metals to specific protein chemisorption sites. Therefore, MLNC were linked to Zn2+ and AnxA1 was added to form MLNC-AnxA1. LNC, MLNC and MLNC-AnxA1 presented average size of 129, 152 and 163 nm, respectively, and similar polydispersity indexes (0.xx); incorporation of chitosan inverted the negative potential zeta; the coordination efficiency of AnxA1 was 92.22 %, and transmission electron microscope photomicrograph showed MLNC-AnxA1 had a spherical shape. The effectiveness of MLNC-AnxA1 was measured in Dextran Sulfate Sodium (DSS)-induced colitis in male C57BL/6 mice. DSS (2 % solution) was administered from days 1-6; saline, LNC, MLNC, MLNC-AnxA1 or AnxA1 were administered, once a day, by oral or intraperitoneal (i.p.) routes, from days 6-9. Clinical parameters of the disease were measured from day 0-10 and gut tissues were collected for histopathology, immunohistochemistry and flow cytometry analyses. Only i.p. treatment with MLNC-AnxA1 reduced weight loss, diarrhea and disease activity index, and prevented loss of colonic structure integrity; induced the switch of macrophages into M2 phenotype in the lamina propria; recovered the colonic histoarchitecture by decreasing dysplasia of crypts, inflammation and ulcerations; restored the expression of claudin-1 Zonna-occludens-1 tight junctions in the inflamed gut; and induced stem cell proliferation in intestinal crypts. Associated, data highlight the functionalization of MLNC with AnxA1 as a tool to improve the local actions of such protein in the inflamed gut by inducing resolution of inflammation and tissue repair.

Development of bozepinib-loaded nanocapsules for nose-to-brain delivery: preclinical evaluation in glioblastoma.

Aim: To develop and characterize bozepinib-loaded lipid-core nanocapsules (BZP-LNC+) as a potential treatment for glioblastoma (GBM). Methods: Characterization of nanocapsules was performed by diameter, polydispersity index, Zeta potential, pH and encapsulation efficiency. GBM cell viability, cell cycle and Annexin/PI were evaluated after BZP-LNC+ treatment. Synergism between BZP-LNC+ and temozolomide (TMZ) was performed by CompuSyn software and confirmed in vitro and in vivo. Results: BZP-LNC+ showed adequate particle sizes, positive Zeta potential, narrow size distribution and high encapsulation efficiency. BZP-LNC+ reduces GBM growth by inducing apoptosis. BZP-LNC+ and TMZ showed synergistic effect in vitro and reduced the in vivo glioma growth by approximately 81%. Conclusion: The present study provides proof-of-principle insights for the combination of these drugs for GBM treatment.

Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications.

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

Nanoformulation Shows Cytotoxicity against Glioblastoma Cell Lines and Antiangiogenic Activity in Chicken Chorioallantoic Membrane.

Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L-1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies.

Folic acid-doxorubicin polymeric nanocapsules: A promising formulation for the treatment of triple-negative breast cancer.

Breast cancer is the most common cancers among women and is one of the main causes of morbidity and mortality in this population. In this study, we aimed to conjugate doxorubicin (DOX), a drug widely used in cancer chemotherapy, and folic acid (FA), a ligand targeted for cancer therapy, to lipid-core nanocapsules (LNC), and evaluate the efficacy of the nanoformulation against triple-negative breast cancer (TNBC) MDA-MB-231 cells that overexpress folate receptors (FRs). We performed cell viability assays, quantitative real-time PCR (qRT-PCR), cell migration assay, and clonogenic assay, as well as measured the levels of nitric oxide (NO) generated and cellular uptake. The results showed that the nanoformulation reduced cell viability. The results of qRT-PCR analysis revealed that the nanoformulation induced apoptosis of MDA-MB-231 cells. The mRNA expression levels of Cat and MnSod were increased when the nanoformulation was compared to the doxorubicin solution. Furthermore, the nanoformulation significantly decreased the migration of breast cancer cells in vitro and inhibited colony formation. Additionally, the expression of iNOS in MDA-MB-231 cells was higher when the nanoformulation was used compared to the doxorubicin solution. Cellular uptake was observed after incubating the MDA-MB-231 cells with the fluorescent-labeled nanoformulation. In conclusion, we developed a promising nanoformulation for the treatment of TNBC. Further studies are necessary to demonstrate the in vivo efficacy of this formulation.

Innovative hydrogel containing polymeric nanocapsules loaded with phloretin: Enhanced skin penetration and adhesion.

Dermatological applications of phloretin are restricted by its poor aqueous solubility. Nanotechnology has been proposed as strategy to increase the apparent drug solubility in aqueous media. This study aimed to develop, characterize, and evaluate the antitumoral effects and safety of polymeric nanocapsules containing phloretin (NCPhl). Further, to incorporate NC-Phl in an innovative semi-solid formulation (HG-NCPhl) to evaluate its performance using porcine skin model. NC-Phl was prepared and the effects in MRC5, HACAT, and SK-mel28 cells were evaluated. Hydrogels were prepared with Lecigel ® and characterized for their nanotechnological properties, adhesion (in vitro washability), and penetration/permeation studies in porcine skin. NC-Phl had a cytotoxic effect against Sk-Mel-28 cells and the population doubling time was increased upon treatment with NC-Phl for longer culture periods; notably when cells were treated for 72 h and then followed for 7 days after the treatment was removed (p < 0.05). HG-NC-Phl was considered adhesive and had a higher capacity to penetrate all skin layers compared with HG-Phl (p < 0.05). The innovative hydrogel HGNC-Phl promoted a drug-reservoir in the stratum corneum and higher penetration of the flavonoid into the epidermis. Therefore, this approach can be considered as a platform to establish versatile dermatological solutions for both cosmeceutics and melanoma therapy.

Folic Acid-Doxorubicin-Double-Functionalized-Lipid-Core Nanocapsules: Synthesis, Chemical Structure Elucidation, and Cytotoxicity Evaluation on Ovarian (OVCAR-3) and Bladder (T24) Cancer Cell Lines.

PURPOSE: Folic acid-doxorubicin-double-functionalized-lipid-core nanocapsules (LNC-CS-L-Zn+2-DOX-FA) were prepared, characterized, and evaluated in vitro against ovarian and bladder cancer cell lines (OVCAR-3 and T24). METHODS: LNC-CS-L-Zn+2-DOX-FA was prepared by self-assembly and interfacial reactions, and characterized using liquid chromatography, particle sizing, transmission electron microscopy, and infrared spectroscopy. Cell viability and cellular uptake were studied using MTT assay and confocal microscopy. RESULTS: The presence of lecithin allows the formation of nanocapsules with a lower tendency of agglomeration, narrower size distributions, and smaller diameters due to an increase in hydrogen bonds at the surface. LNC-L-CS-Zn+2-DOX-FA, containing 98.00 ± 2.34 µg mL-1 of DOX and 105.00 ± 2.05 µg mL-1 of FA, had a mean diameter of 123 ± 4 nm and zeta potential of +12.0 ± 1.3 mV. After treatment with LNC-L-CS-Zn+2-DOX-FA (15 µmol L-1 of DOX), T24 cells had inhibition rates above 80% (24 h) and 90% (48 h), whereas OVCAR-3 cells showed inhibition rates of 68% (24 h) and 93% (48 h), showing higher cytotoxicity than DOX.HCl. The fluorescent-labeled formulation showed a higher capacity of internalization in OVCAR-3 compared to T24 cancer cells. CONCLUSION: Lecithin favored the increase of hydrogen bonds at the surface, leading to a lower tendency of agglomeration for nanocapsules. LNC-CS-L-Zn+2-DOX-FA is a promising therapeutic agent against tumor-overexpressing folate receptors.

Dermatological applications of the flavonoid phloretin.

Botanical molecules are known to have the ability to counteract ultraviolet radiation-induced skin damage. The interest in the development of natural compound-based products for the prevention of solar ultraviolet radiation-induced skin photoaging, melasma, and photocarcinogenesis has been increasing. Recently, the flavonoid phloretin has attracted the attention of researchers in the dermatological field for application in cosmetics and therapeutics. In addition to its antioxidant activity, phloretin has been shown to have properties such as anti-aging and depigmenting effects. In this study, we review the dermatological treatments with phloretin for conditions such as melasma, photoaging, acne, and melanoma. Phloretin has been shown to inhibit elastase and matrix metalloproteinase-1 activity, to reduce cellular tyrosinase activity and melanin content, and induce apoptosis in B16 mouse melanoma 4A5 cells. An in vivo study showed that phloretin, applied topically to the dorsal skin of mice, suppressed the 12-O-tetradecanoylphorbol 13-acetate-induced expression of COX-2, a critical molecular target of many chemopreventive, as well as anti-inflammatory agents. Phloretin can penetrate the skin; nevertheless, its penetration profile in different skin layers has not yet been evaluated. Despite its health benefits, phloretin application has been limited because of its photoinstability and poor aqueous solubility, among other limitations. Therefore, we reviewed the recent advances in pharmaceutical applications such as the use of nanotechnology, in order to improve the cutaneous availability of phloretin. In this review, we also focus on the oral application, product development challenges, and recent progress and future research directions on phloretin.

Erlotinib-Loaded Poly(ε-Caprolactone) Nanocapsules Improve In Vitro Cytotoxicity and Anticlonogenic Effects on Human A549 Lung Cancer Cells.

Lung cancer is the most frequent type of cancer and the leading cause of cancer-related mortality worldwide. This study aimed to develop erlotinib (ELB)-loaded poly(ε-caprolactone) nanocapsules (NCELB) and evaluated their in vitro cytotoxicity in A549 cells. The formulation was characterized in relation to hydrodynamic diameter (171 nm), polydispersity index (0.076), zeta potential (- 8 mV), drug content (0.5 mg.mL-1), encapsulation efficiency (99%), and pH (6.0). NCELB presented higher cytotoxicity than ELB in solution against A549 cells in the MTT and LIVE/DEAD cell viability assays after 24 h of treatment. The main mechanism of cytotoxicity of NCELB was the induction of apoptosis in A549 cells. Further, a significant decrease in A549 colony formation was verified after NCELB treatment in comparison with the unencapsulated drug treatment. The reduction in clonogenic capacity is very relevant as it can reduce the risk of tumor recurrence and metastasis. In conclusion, erlotinib-loaded PCL nanocapsules are promising nanoparticles carriers to increase the efficacy of ELB in lung cancer treatment.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Chitosan-Coated Lipid-Core Nanocapsules Functionalized with Gold-III and Bevacizumab Induced In Vitro Cytotoxicity against C6 Cell Line and In Vivo Potent Antiangiogenic Activity.

PURPOSE: Bevacizumab (BCZ) is a recombinant monoclonal antibody that inhibits the biological activity of the vascular endothelial growth factor, which has an important role in angiogenesis for tumoral growth and progression. In this way, our objective was to develop chitosan-coated lipid-core nanocapsules functionalized with BCZ by an organometallic complex using gold-III. METHODS: The formulation was produced and characterized in relation to physicochemical characteristics. Furthermore, the antitumoral and antiangiogenic activities were evaluated against C6 glioma cell line and chicken embryo chorioallantoic membrane (CAM), respectively. RESULTS: Final formulation showed nanometric size, narrow polydispersity, positive zeta potential and gold clusters size lower than 2 nm. BCZ in aqueous solution (0.01-0.10 µmol L-1) did not show cytotoxic activity in vitro against C6 glioma cell line; although, MLNC-Au-BCZ showed cytotoxicity with a median inhibition concentration of 30 nmol L-1 of BCZ. Moreover, MLNC-Au-BCZ demonstrated cellular internalization dependent on incubation time and BCZ concentration. BCZ solution did not induce significant apoptosis as compared to MLNC-Au-BCZ within 24 h of treatment. CAM assay evidenced potent antiangiogenic activity for MLNC-Au-BCZ, representing a decrease of 5.6 times in BCZ dose comparing to BCZ solution. CONCLUSION: MLNC-Au-BCZ is a promising product for the treatment of solid tumors.

Characterization and antiproliferative activity of glioma-derived extracellular vesicles.

Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment.

Direct effects of poly(ε-caprolactone) lipid-core nanocapsules on human immune cells.

Aim: Poly(ε-caprolactone) lipid-core nanocapsules (LNCs) are efficient drug carriers and drug-free LNCs display therapeutic effects, inhibiting tumor growth and neutrophil activities. Herein, we investigated the direct actions of LNCs on human immune cells, to guide their therapeutic application. Materials & methods: LNC's uptake, cytokine release, cell migration, proliferation and intracellular pathways under inflammatory stimulation were investigated. Results & conclusion: LNCs quickly penetrated leukocytes without cytotoxicity; inhibited mitogen-induced lymphocyte proliferation, cytokine release and leukocyte migration under inflammatory stimulation, which were associated with inhibition of the MAP kinase pathway and intracellular calcium influx. Hence, we showed LNCs as a down-regulatory agent on immune cells, suggesting that either the particles themselves or their application as a drug carrier can halt non-desired inflammatory processes.

Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell.

Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 µM reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype.

Effect on adhesion of a nanocapsules-loaded adhesive system

Abstract This study aimed to evaluate the in situ degree of conversion, contact angle, and immediate and long-term bond strengths of a commercial primer and an experimental adhesive containing indomethacin- and triclosan-loaded nanocapsules (NCs). The indomethacin- and triclosan-loaded NCs, which promote anti-inflammatory and antibacterial effects through controlled release, were incorporated into the primer at a concentration of 2% and in the adhesive at concentrations of 1, 2, 5, and 10%. The in situ degree of conversion (DC, n=3) was evaluated by micro-Raman spectroscopy. The contact angle of the primer and adhesive on the dentin surface (n = 3) was determined by an optical tensiometer. For the microtensile bond strength µTBS test (12 teeth per group), stick-shaped specimens were tested under tensile stress immediately after preparation and after storage in water for 1 year. The data were analyzed using two-way ANOVA, three-way ANOVA and Tukey's post hoc tests with α=0.05. The use of the NC-loaded adhesive resulted in a higher in situ degree of conversion. The DC values varied from 75.07 ± 8.83% to 96.18 ± 0.87%. The use of NCs in only the adhesive up to a concentration of 5% had no influence on the bond strength. The contact angle of the primer remained the same with and without NCs. The use of both the primer and adhesive with NCs (for all concentrations) resulted in a higher contact angle of the adhesive. The longitudinal μTBS was inversely proportional to the concentration of NCs in the adhesive system, exhibiting decreasing values for the groups with primer containing NCs and adhesives with increasing concentrations of NCs. Adhesives containing up to 5% of nanocapsules and primer with no NCs maintained the in situ degree of conversion, contact angle, and immediate and long-term bond strengths. Therefore, the NC-loaded adhesive can be an alternative method for combining the bond performance and therapeutic effects. The use of an adhesive with up to 5% nanocapsules containing indomethacin and triclosan and a primer with no nanocapsules maintained the long-term bond performance.

Anti-inflammatory effect of an adhesive resin containing indomethacin-loaded nanocapsules.

OBJECTIVE: To analyze the anti-inflammatory and analgesic effects of an adhesive resin containing indomethacin-loaded nanocapsules in rat model. DESIGN: Adhesive resin disks with or without indomethacin-loaded nanocapsules were subcutaneously implanted into right hind paw of rats. A week after surgical procedure, 2% formalin solution was intradermally injected into plantar surface of paw. Nociceptive and inflammatory responses were evaluated by formalin test. Paw edema by pletismometer and mechanical hyperalgesia by von Frey test were performed on day 2, day 4, day 6, day 8, day 10 and day 12 after surgery. IL-6, IL-10, and lactate dehydrogenase (LDH) serum levels were determined by ELISA-sandwich test. RESULTS: Group containing indomethacin-loaded nanocapsules (NC) presented lower edema in the right hind paw at 24h after formalin injection than those of the control group (CT) (P<0.01). NC group showed decrease in the nociceptive response in phase I (neurogenic pain) compared to CT group (NC - 66.86±22.83s X CT - 130.17±35.83s, P<0.001). NC group presented supporting higher intensity of stimulus on days 8 and 12 (24h and 72h after formalin injection) (P<0.01 and P<0.02 respectively). The IL-6 serum level was also significantly higher in the NC group than CT group (p<0.001). CONCLUSIONS: These results indicate that an adhesive resin containing indomethacin-loaded nanocapsules has anti-inflammatory and nociceptive activities in a chemical model of acute inflammation. The present investigation confirms an adhesive resin with drug-loaded nanocapsules may be useful for improving therapeutic effect for adhesives to be used in deep cavities.

Nanoencapsulation of chia seed oil with chia mucilage (Salvia hispanica L.) as wall material: Characterization and stability evaluation.

In this study, chia seed oil was nanoencapsulated utilizing chia seed mucilage (CSM) as wall material. The viscosity, encapsulation efficiency, loading capacity, transmission electron microscopy, FT-IR spectroscopy and thermal properties of chia seed oil nanoparticles (CSO-NP) were performed after preparation. Particle size, zeta potential, span value, and pH of CSO-NP and oxidation stability of nanoencapsulated and unencapsulated oil were evaluated during 28days of storage at accelerated conditions (40°C). The CSO-NP showed spherical shape, an average size of 205±4.24nm and zeta potential of -11.58±1.87mV. The encapsulation efficiency (82.8%), loading capacity (35.38%) and FT-IR spectroscopy demonstrated the interaction between oil and mucilage. Furthermore, CSO-NP were thermally stable at temperatures up 300°C and nanoencapsulated oil showed higher stability against oxidation than unencapsulated oil. The results suggest that chia seed mucilage represents a promising alternative to substitute synthetic polymers in nanoencapsulation.