Complexation of oxethazaine with 2-hydroxypropyl-β-cyclodextrin: increased drug solubility, decreased cytotoxicity and analgesia at inflamed tissues

Prado, Andressa R; Yokaichiya, Fabiano; Franco, Margareth K. K. D.; Silva, Camila Morais Gonçalves da; Franz-Montan, Michelle; Volpato, Maria Cristina; Cabeça, Luis Fernando; Paula, Eneida de

doi:10.1111/jphp.12703

Cited by 20 publications

(18 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The slower diffusion of HP-β-CD reflects its larger structure when compared to free CAP. Similar diffusion coefficients for CAP (4.81 × 10 −10 m 2 s −1 ) and HP-β-CD (2.21 × 10 −10 m 2 s −1 ) were reported in the literature [51,52]. Small molecules such as CAP have a high diffusion coefficient, however, when complexed, their diffusion is retarded.…”

Section: Diffusion Ordered Spectroscopy-dosysupporting

confidence: 83%

“…Our group measured F complexed and association constants for the complexation of different LA and CDs, using DOSY-NMR. For the complexation with HP-β-CD and the local anesthetic S-bupivacaine, the F complexed = 57% and Ka = 91 M −1 [49]; and for oxethazaine, F complexed = 38% and Ka = 198 M -1 [51]. Comparing to those LA, the HP-β-CD-CAP complex has a Ka and F complexed notably higher.…”

Section: Diffusion Ordered Spectroscopy-dosymentioning

confidence: 91%

See 1 more Smart Citation

Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues

Couto

Cabeça

Geraldes

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.

show abstract

Section: Diffusion Ordered Spectroscopy-dosysupporting

confidence: 83%

Section: Diffusion Ordered Spectroscopy-dosymentioning

confidence: 91%

Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues

Couto

Cabeça

Geraldes

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In order to enhance the action of RVC aiming at its clinical application, our group has successfully described the use of liposomes and cyclodextrin-based DDS [4,9,19,[22][23][24] . In the development of DDS, analytical methods for the quantification of local anesthetics are required, that allow precise drug determination even in the presence of the carriers.…”

Section: Resultsmentioning

confidence: 99%

Validation of an HPLC Method Devised for the Quantitative Determination of Ropivacaine in Drug-Delivery Systems

Paula¹,

Vieira²,

Franz‐Montan³

et al. 2018

JABST

Self Cite

View full text Add to dashboard Cite

Ropivacaine (RVC) is a long acting local anesthetic, synthesized in the S enantiomeric form. This work describes the development of an analytical method and validation parameters that assured acceptable characteristics (suitability, reliability and feasibility) to quantify RVC in the presence of drug-delivery carriers such as cyclodextrins and liposomes. High performance liquid chromatography (HPLC) was performed using a reversed-phase C18 column, a mixture of acetonitrile and phosphate buffer pH 8.0 (60:40, v: v) as the mobile phase, 1.2 mL/min flow rate and oven temperature of 30 °C; Ropivacaine was detected by UV absorption, at 240 nm. The results showed that the analytical method is accurate, reproducible, robust and linear over the concentration range of 0.08-1.16 mM RVC. The method was applied to detect the in vitro release profile of the anesthetic loaded in two different drug-delivery systems: i) RVC encapsulated into egg phosphatidylcholine liposomes, and ii) RVC complexed with hydroxypropyl-beta-cyclodextrin (HP-βCD). The release kinetics rate was significantly slower for the RVC-HP-βCD complex than for liposomal RVC or the free drug (RVC in solution). To explain that, diffusion ordered spectroscopy (1H-NMR DOSY) experiments were conducted. The results confirmed the stronger interaction of the anesthetic with HP-βCD (association constant, Ka = 128 M-1) than with liposomes (Ka = 22 M-1), in accordance with the release kinetic data. In conclusion, the HPLC method described was proven suitable for the quantification of ropivacaine in drug-delivery systems.

show abstract

“…40 Complexation of drugs with CDs provided an effective approach to enhance the aqueous solubility of poorly soluble drugs thereby improving their therapeutic applications. [41][42][43][44][45][46] Echinomycin is known for the potent antitumor and antimicrobial activity. Interestingly, echinomycin can be intercalated into 5 0 -CG bases in an irreversible manner which interferes with chemoresistance mechanisms.…”

Section: Echinomycin-in-gcd Complex Formation and Characterizationmentioning

confidence: 99%

Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: in vitro anti-proliferative and anti-invasive activity in glioblastoma

et al. 2019

View full text Add to dashboard Cite

show abstract

Complexation of oxethazaine with 2-hydroxypropyl-β-cyclodextrin: increased drug solubility, decreased cytotoxicity and analgesia at inflamed tissues

Abstract: Our results show that complexation improved physicochemical and biological properties of OXZ, allowing its application to inflamed tissues by parenteral routes.

Cited by 20 publications

References 44 publications

Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues

Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues

Validation of an HPLC Method Devised for the Quantitative Determination of Ropivacaine in Drug-Delivery Systems

Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: in vitro anti-proliferative and anti-invasive activity in glioblastoma

Contact Info

Product

Resources

About