Complexation with cyclodextrins (CDs) is a technique that has been extensively used to increase the aqueous solubility of oils and improve their stability. In addition, this technique has been used ...to convert oils into solid materials. This work aims to develop inclusion complexes of
oleoresin (CMO), which presents anti-inflammatory activity, with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) by kneading (KND) and slurry (SL) methods. Physicochemical characterization was performed to verify the occurrence of interactions between CMO and the cyclodextrins. Carrageenan-induced hind paw edema in mice was carried out to evaluate the anti-inflammatory activity of CMO alone as well as complexed with CDs. Physicochemical characterization confirmed the formation of inclusion complex of CMO with both β-CD and HP-β-CD by KND and SL methods. Carrageenan-induced paw edema test showed that the anti-inflammatory activity of CMO was maintained after complexation with β-CD and HP-β-CD, where they were able to decrease the levels of nitrite and myeloperoxidase. In conclusion, this study showed that it is possible to produce inclusion complexes of CMO with CDs by KND and SL methods without any change in CMO's anti-inflammatory activity.
Chronic venous insufficiency is characterized by chronic reflux disorder of blood from the peripheral to the central vein, with subsequent venous hypertension and resulting changes in the skin. ...Traditionally, nonsurgical treatments relied on the use of compression therapy, and more recently a variety of flavonoids have been shown to have positive effects. There have also been developments of more effective drug delivery systems using various textiles and nanotechnology to provide new therapeutic options. Our objective was to use nanotechnology to develop a new formulation containing hesperetin (Hst), a substance not previously used in the treatment of chronic venous insufficiency, impregnated into textile fibers as a possible alternative treatment of venous diseases. We prepared the nanocapsules using the interfacial deposition of preformed polymer method with an Hst concentration of 0.5 mg/mL and then characterized the size and distribution of particles. To quantify the Hst in the samples, we developed an analytical method using high-performance liquid chromatography. Studies of encapsulation efficiency (98.81%±0.28%), microscopy, drug release (free-Hst: 104.96%±12.83%; lipid-core nanocapsule-Hst: 69.90%±1.33%), penetration/permeation, drug content (0.46±0.01 mg/mL) and the effect of washing the textile after drug impregnation were performed as part of the study. The results showed that nanoparticles of a suitable size and distribution with controlled release of the drug and penetration/permeation into the skin layers were achieved. Furthermore, it was established that polyamide was able to hold more of the drug, with a 2.54 times higher content than the cotton fiber; after one wash and after five washes, this relation was 2.80 times higher. In conclusion, this is a promising therapeutic alternative to be further studied in clinical trials.
Venous ulcers are a more severe complication of chronic venous insufficiency, significantly compromising patient quality of life (QoL). Compressive stockings are still the gold standard treatment ...method with alternative therapies currently being evaluated. In this perspective, we investigate the influence of compressive stockings impregnated with hesperetin-based nanocapsules in the healing process of venous ulcers. Compressive stockings impregnated with hesperetin-based nanocapsules were applied to a consenting patient for 6 months following all relevant ethical principles for patient studies. The patient was evaluated at baseline (T0), 3 months (T3), and 6 months (T6), using photographic register (healing) probes to measure skin melanin, erythema and hydration parameters, and venous diameters, followed by questionnaires regarding QoL and pain perception. Healing was observed at the 3-month time point and with 91.6% and 93.1% of retraction area in larger ulcers of the right leg and lateral portion of the left leg, respectively. The deepest ulcer in a medial portion of the left leg healed 47.3%. A reduction of all measured skin parameters was observed, indicating a possible hesperetin effect. The scores of QoL and pain were, respectively, in the ranges of 91.6 to 31.2 and 7 to 0. Reduction in venous diameters also indicates healing function. These preliminary findings suggest that compressive stockings impregnated with hesperetin nanocapsules enhance venous ulcer healing. Further clinical trial controlled by placebo, involving a greater number of patients, is required to confirm the findings of this case report.
•β-cyclodextrin/myrtenol (β-CD/MYR) complex was done by slurry complexation method.•β-CD/MYR complex reduced mechanical hyperalgesia in animal model.•β-CD/MYR complex showed anxiolytic-like effect in ...animal model of fibromyalgia.•β-CD/MYR complex prevented cognitive impairment caused by acid saline injection.•These effects seemed to be related to the maintenance of redox homeostasis.
Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with β-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into β-cyclodextrin cavity. The interaction between myrtenol and β-cyclodextrin was confirmed by molecular docking. Hence, the SC β-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and β-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the β-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, β-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.
Carvacrol is a good natural antimicrobial and antioxidant agent; however, its poor aqueous solubility and high volatility limit its application in food systems. Different methods of complexation have ...been used to preserve aromas in food products and complexation in cyclodextrins (CDs) is among the most efficient ways. In the present study, we investigated the complexation efficiency of carvacrol in β-CD using methods different from those already reported in the literature for this compound. The supramolecular structure of the carvacrol/β-CD complex was investigated by means of X-ray diffraction (XRD), Nuclear magnetic resonance (NMR), docking, complexation efficiency, thermogravimetry/derivate thermogravimetry (TG/DTG) and Karl Fischer titration. Results clearly showed the formation of a supramolecular complex in which the guest molecule, carvacrol, was entrapped inside the cavity of the host, β-CD mainly by slurry method. These results contribute to other studies involving this type of system.
Display omitted
•Carvacrol is an important compound for the food and pharmaceutical industry.•The monoterpenoid has a poor water solubility and this limits its utilization.•The inclusion complex between β-cyclodextrin and carvacrol improves the physico-chemical characteristics of monoterpene.•The inclusion complex increases the carvacrol utilization in biological systems.
Oral infections are associated with the appearance of systemic diseases. Among the natural products, commercially used in dental formulations is thymol (TM). However, this compound presents low ...stability. In order to overcome these limitations, the membranes were prepared using the solvent evaporation method and TM/β-cyclodextrin using the liofilization technique. The results showed that the presence of inclusion complex in the membranes causes considerable modifications in the physical-chemical, morphological, and mucoadhesive properties. In addition, the membranes presented antimicrobial activity. These data show that mucoadhesive membranes containing IC may be promising systems for TM delivery in the treatment of oral infections.
ABBREVIATIONS
β-CD: β-cyclodextrin, TM: Thymol, IC: Inclusion complex, XRD: X-ray diffraction, ATR-FTIR: Attenuated Total Reflectance-Fourier Transform Infrared, SEM: Scanning electron microscopy, DSC: Differential Scanning Calorimetry, TG: Thermogravimetry, Propylene glycol (PPG).
There is considerable interest in the pharmaceutical and biomedical areas in the use of sponges, produced with biopolymers, as matrices for the controlled release of drugs. The objective of this work ...was to evaluate the physicochemical characterization of alginate–gelatin (ALG–GEL) sponges containing usnic acid (UA), by thermogravimetric analysis (TG/DTG), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The macroscopic aspect showed a flexible structure, with variations in coloration depending on the concentration of UA in the sponges. The TG/DTG curves of ALG–GEL sponges and sponges containing 1 and 5 % of UA showed similar profiles and percentages of loss of mass. The DSC curves of both the sponges showed similar profiles, with two events involving a variation of enthalpy being observed, the first an endothermic event and the latter exothermic events, typical of decomposition. These curves show the absence of an endothermic peak of UA at 201 °C, indicating that the drug was present in the polymeric system. The SEM showed the ALG–GEL sponge to have the largest average pore diameter and a more heterogeneous arrangement of polymeric fibers, while sponges incorporated with UA showed more homogeneous arrangement of polymeric fibers. In conclusion, the incorporation of UA did not change the thermal stability of the sponges. Furthermore, the sponges incorporated with the drug showed a microstructural organization suitable for drug release systems.
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.
Abstract The hepatoprotective effect of P. leschenaultii . (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400 mg/kg) were administered ...daily via gavage for 14 days before paracetamol (2000 mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.
Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory ...or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with β-cyclodextrin (βCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-βCD (50 mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in βCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-βCD reduced (p < 0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-βCD inhibited (p < 0.05) TNF-α production in the spinal cord and stimulated (p < 0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-βCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-βCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in βCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.
•BIS and BIS-βCD reduced mechanical and thermal hyperalgesia in inflammatory and neuropathic pain.•BIS and BIS-βCD inhibited TNF-α production in the spinal cord and stimulated the release of IL-10 in the spinal cord in PLSN-mice.•BIS and BIS-βCD reduced IBA-expression in the spinal cord in the PLSN model.
PDF
