Monoketonic Curcuminoid Lidocaine Co Deliver Using Thermosensitive Organogels From Drug Synthesis to Epidermis Structural Studies

Organogels ORGs are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug carrier systems, considering the application of synthetic monoketonic curcuminoid m CUR and lidocaine LDC to treat topical inflammatory lesions. The monoketone curcuminoid m CUR was synthesized by using an innovative method via a NbCl5 acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate IPM , soy lecithin LEC , and the synthesized m CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m CUR shifted the sol gel transition temperature, and that the addition of LDC enhanced the rheological G amp; 8242; G amp; 8243; ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy FTIR , where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography OCT analysis revealed that LEC and m CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin deliver

Evaluation of budesonide-hydroxypropyl-β-cyclodextrin inclusion complex in thermoreversible gels for ulcerative colitis

Background: New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-β-CD) and poloxamers (PL) were developed for future clinical use. Aims: This study evaluated the efficacy of such novel formulations in a rat model of colitis. Methods: The PL-BUDHP-β-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL−1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUDHP-β-CD + PL407 (18%); BUD 2: BUDHP-β-CD + PL407 (20%); BUD 3: BUDHP-β-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-β-CD; C1: HP-β-CD + PL407 (18%); C2: HP-β-CD + PL407 (20%); C3: HP-β-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1β, IL-10 and endogenous glucocorticoids were obtained using ELISA. Results: BUDHP-β-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-β-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-β-CD (p < 0.01). All formulations with BUDHP-β-CD poloxamers reduced TNF-α levels (p < 0.05). Conclusion: Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2014/26200-

Sufentanil-2-hydroxypropyl-β-cyclodextrin Inclusion Complex For Pain Treatment: Physicochemical, Cytotoxicity, And Pharmacological Evaluation

Sufentanil (SUF) is a synthetic analgesic opioid widely used for the management of acute and chronic pain. This drug was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the physicochemical characterization, in vitro/ex vivo toxicity assays, and pharmacological evaluation were performed. Differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR) analysis, and X-ray powder diffraction showed the formation and the morphology of the complex. Nuclear magnetic resonance afforded data regarding inclusion complex stoichiometry (1:1) with an association binding constant (Ka) value of 515.2 ± 1.2M-1 between SUF and HP-β-CD. Complexation with HP-β-CD protected SUF from light exposure and increased its photostability. Release kinetics revealed a decrease in SUF release rate (Krel = 7.05 ± 0.52 and 5.61 ± 0.39min-1/2 for SUF-HP-β-CD and SUF, respectively) and reduced hemolytic or myotoxic effects after complexation. Time course of tail-flick test showed that the duration of analgesia induced by SUF (150.0 ± 34.6min) was significantly increased (p < 0.001) after complexation with HP-β-CD (355.7 ± 47.2min) when injected at the same dose (1μg kg-1), prolonging the duration of analgesia after intramuscular administration and representing an alternative on the development of effective and safe drug-delivery system for opioid analgesics. © 2012 Wiley Periodicals, Inc.1011036983707Slingsby, L.S., Murison, P.J., Goossens, L., Engelen, M., Waterman-Pearson, A.E., A comparison between pre-operative carprofen and a long-acting sufentanil formulation for analgesia after ovariohysterectomy in dogs (2006) Vet Anaesth Analg, 33, pp. 313-327Meert, T.F., Pharmacotherapy of opioids: Present and future developments (1996) Pharm World Sci, 18, pp. 1-15Meert, T.F., Mesens, J., Verheyen, P., Noorduin, H., Hydroxypropyl-beta-cyclodextrin can modulate the activity of spinally administered sufentanil (1992) Eur J Anaesthesiol, 9, pp. 399-409Yaksh, T.L., Jang, J.D., Nishiuchi, Y., Braun, K.P., Goodman, M., The utility of 2-hydroxypropyl-beta-cyclodextrin as a vehicle for the intracerebral and intrathecal administration of drugs (1992) Life Sci, 48, pp. 623-633Jang, J., Yaksh, T.L., Hill, H.F., Use of 2-hydroxypropyl-β-cyclodextrin as an intrathecal drug vehicle with opioids (1992) J Pharm Exp Ther, 261, pp. 592-600Meert, T.F., Melis, W., Interactions between epiduraly and intrathecally administered sulfentanil and bupivacaine in hydroxypropyl-β-cyclodextrin in the rat (1992) Acta Anaesthesiol Scand, 43, pp. 79-89Holvoet, C., Plaizier-Vercammen, J., Vander Heyden, Y., Gabriels, M., Camu, F., Preparation and in vitro release rate of fentanyl-cyclodextrin complexes for prolonged action in epidural analgesia (2003) Int J Pharm, 265, pp. 13-26Ogawa, N.O., Higashi, K., Nagase, H., Endo, T., Moribe, K., Loftsson, T., Yamamoto, K., Ueda, H., Effects of cogrinding with β-cyclodextrin on the solid state fentanyl (2010) J Pharm Sci, 99, pp. 5019-5029Waldeck, A.R., Kuchel, P.W., Lennon, A.J., Chapman, B.E., NMR diffusion measurements to characterize membrane transport and solute binding (1997) Prog Nucl Magn Reson Spectrosc, 30, pp. 39-68Fraceto, L.F., Moraes, C.M., Abrami, P., Gonçalves, M.M., Andreo, F.N., Fernandes, S.A., de Paula, E., Preparação e caracterização Físico-química de complexos de inclusão entre anestésicos locais e hidroxipropilbeta-ciclodextrina (2007) Quim Nova, 30, pp. 777-784Wimmer, R., Aachamann, F.L., Larsen, K.L., Petersen, S.B., NMR diffusion as a novel tool for measuring the association constant between cyclodextrin and guest molecules (2002) Carbohydr Res, 337, pp. 841-849de Araujo, D.R., Tsuneda, S.S., Cereda, M.S., Carvallho, F.D.G.E., Preté, P.S.C., Fernandes, S.A., Yokaichiya, F., de Paula, E., Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-β-cyclodextrin inclusion complex (2008) Eur J Pharm Sci, 33, pp. 60-71Grillo, R., de Melo, N.F., Moraes, C.M., de Lima, R., Menezes, C.M., Ferreira, E.I., Rosa, A.H., Fraceto, L.F., Study of the interaction between hydroxymethylnitrofurazone and 2-hydroxypropyl-beta-cyclodextrin (2008) J Pharm Biomed Anal, 47, pp. 295-302Lambropoulos, J., Spanos, G.A., Lazaridis, N.V., Development and validation of an HPLC assay for fentanyl, alfentanil, and sufentanil in swab samples (2000) J Pharm Biomed Anal, 23, pp. 421-428Kranz, H., Brazeau, G.A., Napaporn, J., Martin, R.L., Millard, W., Bodmeier, R., (2001) Int J Pharm, 212, pp. 11-18. , Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systemsMalheiros, S.V.P., Pinto, L.M.A., Gottardo, L., Yokaichiya, D.K., Fraceto, L.F., Meirelles, N.C., de Paula, E., A new look at the hemolytic effect of local anesthetics considering their real membrane/water partitioning at pH 7.4 (2004) Biophys Chem, 110, pp. 213-221Johnson Jr., C.S., Diffusion ordered nuclear magnetic resonance spectroscopy: Principles and applications progress in nuclear magnetic resonance (1999) Spectroscopy, 34, pp. 203-256Bakkour, Y., Vermeersch, G., Morcellet, M., Boschin, F., Martel, B., Azaroual, N., Formation of cyclodextrin inclusion complexes with doxycyclin-hyclate: NMR investigation of their characterization and stability (2006) J Incl Phenom Macrocycl Chem, 54, pp. 109-114Giordano, F., Novak, C., Moyano, J.R., Thermal analysis of cyclodextrins and their inclusion compounds (2001) Thermochim Acta, 380, pp. 123-151Yap, K.L., Liu, X., Thenmozhiyal, J.C., Ho, P.C., Characterization of the 13-cis-retinoic acid/cyclodextrin inclusion complexes by phase solubility, photostability, physicochemical and computational analysis (2005) Eur J Pharm Sci, 25, pp. 49-56Costa, P., Lobo, J.M.S., Modeling and comparison of dissolution profiles. 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USING SUCROSE FOR THE GLUCOSE TOLERANCE TEST DETERMINATION IN BIOCHEMISTRY CLASSES

The development of enzymatic, portable, non-expensive kits for glucose dosage allowed this test to beconducted outside the laboratory. Besides, the increasing number of diabetic patients making use ofthese kits turn their prices quite aordable, nowadays. In a previous work we have reported the use ofglucose kits inside the classroom, for the Glucose Tolerance Tests determination, in association withaerobic exercises, as a starting point to teach metabolism (Alves, A.A. et al., Annals of the XXIXSBBq Meeting, 2000). That experience has been successfully employed in the last ve years withstudents from careers such as Biology, Physical Education, Nursing and Medicine, at Unicamp. Wenow extend those observations to the use of sucrose, instead of glucose, as the sugar given in overchargeat the beginning of the experiment (1.15 and 2.3 g/kg weight for glucose and sucrose, respectively).Portable reectance meters provided accurate enzymatic measurement of glucose with a drop of blood.Since the enzyme (glucose oxydase) is specic for glucose (and not for fructose, for instance), the plotsobtained after sucrose intake are very similar to those with glucose. The advantages in using sucroseare: it is cheaper than glucose and suitable for the use outside the lab (easy to nd) and it does notinduce the characteristic unsettled stomach/nausea caused by glucose. Besides, the use of sucrosedoes not invalidate the classical use of the test, since sucrose is cleaved by invertase (giving rise toglucose and fructose) in the duodenum, where glucose units can be absorbed, giving rise the bloodprole evaluated in the tolerance test