betadex and Edema

Inflammatory arthritis is the most prevalent chronic inflammatory disease worldwide. The pathology of the disease is characterized by increased inflammation and oxidative stress, which leads to chronic pain and functional loss in the joints. Conventional anti-arthritic drugs used to relieve pain and other arthritic symptoms often cause severe side effects. α-bisabolol (BIS) is a sesquiterpene that exhibits high anti-inflammatory potential and a significant antinociceptive effect. This study evaluates the anti-arthritic, anti-inflammatory and antihyperalgesic effects of BIS alone and in a β-cyclodextrin (βCD/BIS) inclusion complex in a CFA-induced arthritis model. Following the intra-articular administration of CFA, male mice were treated with vehicle, BIS and βCD/BIS (50 mg/kg, p.o.) or a positive control and pain-related behaviors, knee edema and inflammatory and oxidative parameters were evaluated on days 4, 11, 18 and/or 25. Ours findings shows that the oral administration of BIS and βCD/BIS significantly attenuated spontaneous pain-like behaviors, mechanical hyperalgesia, grip strength deficit and knee edema induced by repeated injections of CFA, reducing the joint pain and functional disability associated with arthritis. BIS and βCD/BIS also inhibited the generation of inflammatory and oxidative markers in the knee and blocked MAPK in the spinal cord. In addition, ours results also showed that the incorporation of BIS in cyclodextrin as a drug delivery system improved the pharmacological profile of this substance. Therefore, these results contribute to the pharmacological knowledge of BIS and demonstrated that this terpene appears to be able to mitigate deleterious symptoms of arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; beta-Cyclodextrins; Chronic Pain; Disease Models, Animal; Edema; Hyperalgesia; Interleukin-1beta; Interleukin-6; Male; Mice; Monocyclic Sesquiterpenes

Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work,

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Anti-Inflammatory Agents; Antioxidants; beta-Cyclodextrins; Edema; Euterpe; Female; In Vitro Techniques; Male; Mice; Phytochemicals; Plant Oils; Plants, Medicinal

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/β-cyclodextrin (β-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with β-CD alone and β-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:β-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Calorimetry, Differential Scanning; Carrageenan; Crystallization; Drug Compounding; Edema; Excipients; Flufenamic Acid; Male; Microwaves; Polyethylene Glycols; Polyvinyls; Rats; Rats, Wistar; Solubility

Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active.

Topics: Animals; beta-Cyclodextrins; Biological Availability; Caffeic Acids; Carrageenan; Disease Models, Animal; Drug Stability; Edema; Rats; Solubility; Spectroscopy, Fourier Transform Infrared; Treatment Outcome

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development.

Topics: Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Brazil; Edema; Female; Humans; Male; Mice; Ocimum basilicum; Oils, Volatile; Plant Extracts

The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Topical; Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Carbazoles; Cattle; Edema; Female; Freeze Drying; Humans; In Vitro Techniques; Lactic Acid; Male; Mice; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Skin; Swine; Tetradecanoylphorbol Acetate

Staphylococcus aureus infection of the anterior chamber can occur after cataract surgery, causing inflammation and extensive damage to the iris. Alpha-toxin, the most potent S. aureus corneal toxin, was tested as a possible mediator of damage to the iris, and alpha-toxin anti-serum and a chemical toxin inhibitor were tested as potential pathology-reducing agents.. The hemolytic activity of alpha-toxin and its inhibition by a chemical inhibitor or anti-serum were quantified in vitro. Purified alpha-toxin, heat-inactivated toxin, or alpha-toxin plus normal serum, alpha-toxin anti-serum, or the chemical inhibitor, methyl-β-cyclodextrin-cholesterol (CD-cholesterol), was injected into the rabbit anterior chamber. Pathological changes were photographed, quantified by slit-lamp examination (SLE) scoring, and further documented by histopathological analysis.. At five hours post-injection, eyes injected with alpha-toxin or heat-inactivated toxin had a mean SLE score of 7.3 ± 0.59 or 0.84 ± 0.19, respectively. Active toxin caused moderate to severe iris edema, severe erosion of the iris, and mild to moderate fibrin accumulation in the anterior chamber. Alpha-toxin plus anti-serum or CD-cholesterol, in contrast to alpha-toxin alone, caused less iris edema and epithelium sloughing as well as significantly lower SLE scores than eyes receiving alpha-toxin alone (p ≤ 0.019).. Alpha-toxin caused extensive iris damage and inflammation, and either anti-alpha-toxin anti-serum or CD-cholesterol was able to significantly reduce toxin-mediated damage and inflammation.

Topics: Animals; Anterior Chamber; Antibodies, Blocking; Bacterial Toxins; beta-Cyclodextrins; Cholesterol; Complement Hemolytic Activity Assay; Drug Combinations; Edema; Exotoxins; Hemolysin Proteins; Injections, Intraocular; Iris; Iris Diseases; Neovascularization, Pathologic; Rabbits; Slit Lamp

Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acrylates; Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; beta-Cyclodextrins; Edema; Gels; Inflammation; Male; Methylcellulose; Nanoparticles; Ointments; ortho-Aminobenzoates; Particle Size; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility

Nimesulide (NIM) is an insoluble nonsteroidal anti-inflammatory drug (NSAID). Complexation of drug with methyl β-cyclodextrin was evaluated to improve solubility and dissolution rate of NIM. Complexation was achieved via a coevaporation technique to obtain different drug to polymer molar ratios (1:1, 1:2, and 1:3). The physicochemical characterization of the systems using powder X-ray diffraction and infrared spectroscopy was carried out to understand the influence of this technological process on the physical status of single components and complex systems and to detect possible interactions between drug and carrier. Moreover, quantitative solubility and in vitro dissolution studies of NIM alone and NIM inclusion complexes were studied in the dissolution media of phosphate buffer pH 5.5 and 7.4. The analysis provided existence of a molecular interaction between drug and carrier together in the complex state. The study showed that the inclusion systems enhanced of drug solubility, dissolution rate, and anti-inflammatory activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Disease Models, Animal; Drug Carriers; Drug Liberation; Edema; Rats; Solubility; Sulfonamides; Technology, Pharmaceutical

Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26-30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/β-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/β-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/β-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with β-CD improved analgesic and anti-inflammatory effects of p-cymene.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; beta-Cyclodextrins; Carrageenan; Cymenes; Drug Evaluation, Preclinical; Edema; Hot Temperature; Macromolecular Substances; Male; Mice; Monoterpenes; Pain Measurement; Phytotherapy; Time Factors

New compounds of β-cyclodextrin containing covalently bound (conjugated) residues of acetylsalicylic and 1-(4-isobutylphenyl)-propionic acids were synthesized in the reaction of chlorides of the corresponding acids with β-cyclodextrin. We studied antiplatelet and antiphlogistic properties of these substances. It was shown that new compounds are comparable and in some cases are superior to the reference drugs acetylsalicylic acid and ibuprofen by anti-inflammatory and antiaggregant activities.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; beta-Cyclodextrins; Edema; Ibuprofen; Mice; Molecular Structure; Platelet Aggregation; Propionates; Structure-Activity Relationship

In our work depot delivery systems of celecoxib were developed using multivesicular liposomes. Moreover, the solubility of celecoxib was enhanced by complexing drug with cyclodextrin to overcome the limitation of conventional therapy. The multivesicular liposomes (MVLs) bearing celecoxib-beta -cyclodextrin inclusion complex were prepared by reverse phase evaporation method, and multilamellar vesicles (MLVs)-bearing drug complex was prepared by the cast film method. The formulations were characterized for vesicle size, encapsulation efficiency, and in vitro drug release. In vivo performance of multivesicular liposomes bearing celecoxib-beta -cyclodextrin inclusion complex was evaluated by assessing anti-inflammatory activity using carrageenan-induced rat paw edema volume method. The results were compared with that of celecoxib-cyclodextrin complex and MLVs containing celecoxib-beta -cyclodextrin inclusion complex in equal amounts. Phase solubility studies for the celecoxib-beta -cyclodextrin inclusion complex clearly indicated an increase in aqueous solubility of celecoxib with an increase in beta -CD concentration. The in vitro release studies reveal that MLVs release more than 80% drug within 48 hr whereas MVL formulations release nearly the same amount of drug in 120 hr. In vivo data reveal that reduction in paw volume with MVL formulation was not rapid and fast, but the effect was maintained for prolonged periods, and even after 24 hr there was 40.7 +/- 3.40% reduction in paw volume. MVL formulation showed more sustained and prolonged anti-inflammatory effect compared with plain drug and MLVs. We concluded that multivesicular liposome can be successfully utilized for the sustained delivery of celecoxib.

Topics: Administration, Cutaneous; Animals; beta-Cyclodextrins; Carrageenan; Celecoxib; Chemistry, Pharmaceutical; Cyclooxygenase 2 Inhibitors; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Edema; Female; In Vitro Techniques; Liposomes; Male; Particle Size; Permeability; Pyrazoles; Rats; Skin Absorption; Solubility; Sulfonamides

Dextran, mannan and carboxymethylcellulose, previously activated by periodate oxidation, were grafted with beta-cyclodextrin moieties by reductive alkylation in the presence of sodium borohydride. These polymers were used as supramolecular carriers for naproxen, improving the "in vivo" anti-inflammatory properties of this drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Carcinogens; Carrageenan; Dextrans; Drug Carriers; Edema; Male; Mannans; Naproxen; Oxidation-Reduction; Periodic Acid; Rats; Rats, Wistar

Superoxide dismutase was glycosidated with cyclodextrin-branched carboxymethylcellulose. The modified enzyme contained 1.4 mol polymer per mol protein and retained 87% of the initial activity. The anti-inflammatory activity of superoxide dismutase was 2.2-times increased after conjugation and its plasma half-life time was prolonged from 4.8 min to 7.2 h.

Topics: Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Carrageenan; Cyclodextrins; Edema; Foot; Male; Rats; Rats, Wistar; Superoxide Dismutase

The purpose of this study was 1) to investigate in vivo advantages of a flurbiprofen (FPN)-hydroxypropyl beta-cyclodextrin (HPbetaCD) solid dispersion (SD) in rats, 2) to study factors affecting the drug release from SD formulations, and 3) to evaluate the pharmacokinetic profile of the drug when administered as SD, in humans. The solubility of FPN in water and dissolution media was evaluated as a function of HPbetaCD concentration. The SD was prepared by coevaporation from dilute aqueous NH3 and evaluated in rats. The release of the drug from tablet formulations and capsules of SD was studied in simulated gastric fluid and phosphate buffer, pH 7.2. The bioavailability of drug when administered as SD was evaluated in humans. HPbetaCD enhanced the solubility of the drug, and SD improved bioavailability and reduced ulcerogenicity of the drug in rats. The type of excipient used affected drug release from tablets. Presence of microcrystalline cellulose, a hydrophilic polymeric excipient, resulted in uptake of water and stabilization of the resulting gels-like structure of HPbetaCD-containing tablets. This adversely affected drug release. The release from capsules filled with SD was comparable to that obtained from plain SD powder. The drug-HPbetaCD association constant in water was much lower than the values reported in literature. The bioavailability (which could suffer in case of higher association constant) was enhanced on administration of SD-filled capsules to humans.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cross-Over Studies; Drug Evaluation, Preclinical; Edema; Flurbiprofen; Humans; Male; Rats; Rats, Wistar

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cyclodextrins; Edema; Intestinal Mucosa; Male; Meloxicam; Rats; Rats, Wistar; Stomach Ulcer; Thiazines; Thiazoles

4-Biphenylacetic acid, a potent non-steroidal anti-inflammatory agent forms a solid inclusion complex with beta-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2.9 mg kg-1 for the complex and of 6.2 mg kg-1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Carrageenan; Cyclodextrins; Edema; Male; Phenylacetates; Rats; Rats, Inbred Strains; Stomach Ulcer

Ethyl 4-biphenylyl acetate (EBA) is a prodrug of the antiinflammatory 4-biphenylyl acetic acid (BPAA). The inclusion complexes of EBA with beta-cyclodextrin (beta-CyD), heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD), and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) at a molar ratio of 1:2 (EBA:cyclodextrin) were prepared and used to make hydrophilic antiinflammatory ointments. The in vitro release of EBA from the ointments was enhanced by complexation in the order of beta-CyD less than DM-beta-CyD less than or equal to HP-beta-CyD. The improvement correlated with the improved solubility and not with the decreased diffusibility observed to occur upon the complexation of EBA. In vivo the complexation with cyclodextrin derivatives increased both the release of EBA from the vehicle and its conversion in the underlying tissue to BPAA, but the total of EBA and BPAA in the tissue was decreased. In vitro studies confirmed that the effects of cyclodextrin derivatives on the conversion were exerted indirectly. The combination of the enhanced release and of the enhanced prodrug hydrolysis by esterases in the site where the antiinflammatory action is required resulted in increased therapeutic effects. In the model of carrageenan-induced acute edema in rat paw, the complexation improved the therapeutic effects over those of EBA alone in the order of beta-CyD less than DM-beta-CyD less than HP-beta-CyD. HP-beta-CyD may be a particularly useful cyclodextrin derivative since it improves the topical availability and does not irritate tissues.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Biotransformation; Carrageenan; Chromatography, High Pressure Liquid; Cyclodextrins; Edema; Hydrolysis; Male; Ointments; Phenylacetates; Prodrugs; Rats; Rats, Inbred Strains; Skin Absorption; Solubility