Study to explore inclusion complexes of α- and β-cyclodextrin molecules with 3-octyl-1-methylimidazolium bromide with the manifestation of hydrophobic and hydrophilic interactions

Sarkar, Kalipada; Barman, Biraj Kumar; Roy, Mahendra Nath

doi:10.1016/j.cplett.2018.07.019

Cited by 10 publications

(4 citation statements)

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“…A small shift towards lower wavelengths of about 3 nm was also evident. These effects are due to the variation in the local polarity caused by the accommodation of the IDE molecules within the apolar cavity of the macrocycle, and they are due to the formation of new hydrophobic–hydrophobic interactions [ 45 ]. Due to the large extension of the ACyD8 cavity, produced by the presence of octanoyl chains on both rims of the macrocycle, the total inclusion of the drug within the cavity is conceivable.…”

Section: Resultsmentioning

confidence: 99%

“…UV-vis data were used to determine the apparent binding constant (Kc) of the 1:1 IDE/ACyD8 inclusion complex on the basis of the Benesi–Hildebrand equation [ 45 ]. A linear relationship (R 2 = 0.9882) was obtained for the plot of 1/A-A 0 versus 1/[ACyD8] ( Figure 3 ), but not for the plot of 1/A-A 0 versus 1/[ACyD8] 2 (R 2 = 0.9676) (plot not shown) demonstrating the presence in solution of a 1:1 inclusion complex.…”

Section: Resultsmentioning

confidence: 99%

“…UV-vis data were employed to determine the apparent binding constant (Kc) of the IDE/ACyD8 inclusion complex by means of the Benesi–Hildebrand equations given below [ 45 , 52 ]. 1/(A-A 0 ) = 1/(Δε Kc [ACyD8] n ) + 1/Δε where A-A 0 is the difference in the absorbance of IDE in the presence and absence of the macrocycle, Δε is the molar absorption coefficient of IDE, and Kc is the association constant.…”

Section: Methodsmentioning

confidence: 99%

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Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study

et al. 2023

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Idebenone (IDE), a synthetic short-chain analogue of coenzyme Q10, is a potent antioxidant able to prevent lipid peroxidation and stimulate nerve growth factor. Due to these properties, IDE could potentially be active towards cerebral disorders, but its poor water solubility limits its clinical application. Octanoyl-β-cyclodextrin is an amphiphilic cyclodextrin (ACyD8) bearing, on average, ten octanoyl substituents able to self-assemble in aqueous solutions, forming various typologies of supramolecular nanoassemblies. Here, we developed nanoparticles based on ACyD8 (ACyD8-NPs) for the potential intranasal administration of IDE to treat neurological disorders, such as Alzheimer’s Disease. Nanoparticles were prepared using the nanoprecipitation method and were characterized for their size, zeta potential and morphology. STEM images showed spherical particles, with smooth surfaces and sizes of about 100 nm, suitable for the proposed therapeutical aim. The ACyD8-NPs effectively loaded IDE, showing a high encapsulation efficiency and drug loading percentage. To evaluate the host/guest interaction, UV-vis titration, mono- and two-dimensional NMR analyses, and molecular modeling studies were performed. IDE showed a high affinity for the ACyD8 cavity, forming a 1:1 inclusion complex with a high association constant. A biphasic and sustained release of IDE was observed from the ACyD8-NPs, and, after a burst effect of about 40%, the release was prolonged over 10 days. In vitro studies confirmed the lack of toxicity of the IDE/ACyD8-NPs on neuronal SH-SY5Y cells, and they demonstrated their antioxidant effect upon H2O2 exposure, as a general source of ROS.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study

et al. 2023

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“…or tyramine (1-10 mM) in D 2 O (Sigma-Aldrich), while the B-CD concentration was kept constant at 11 mM. Samples were analyzed using 1 H-NMR (400 mHz, Bruker, Leiderdorp, NL) and an association constant (K a ) was calculated 393,394 . Dd max was calculated as (1/ intercept), after which the K a was calculated as (1/(slope*Dd max ).…”

Section: Affinity Assay By 1 H Nmr Of Bupivacaine and Tyramine For B-cdmentioning

confidence: 99%

Postoperative skeletal pain

Steverink¹

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This thesis attempts to better understand postoperative skeletal pain, quantify its severity and provide directions for its improved treatment. Chapter 2 described the current clinical practice in patients undergoing spine surgery regarding postoperative pain and its treatment. Most patients developed moderate opioid-related adverse drug events (ORADEs) while still experiencing pain. To understand the severity of postoperative skeletal pain, an immunohistochemical study quantifying bone sensory innervation was performed on human bone samples from various anatomical locations in Chapter 3. The highest sensory innervation density was found in the periosteum. The anatomical location receiving most sensory innervation was the thoracic spine. Chapter 4 consists of a literature review on bone pain. This chapter identified four pathways involved in generation and maintenance of bone pain. These pathways were the activation, sensitization and sprouting of sensory nerve fibers as well as central sensitization. The high incidence of postoperative ORADEs illustrated the delicate balance between analgesic and side effects of current postoperative pain treatment. Its dense innervation identified the periosteum as a source of pain and potential target for postoperative analgesia. The second aim was to assess the safety and efficacy of a non-opioid anesthetic (bupivacaine) when applied in high concentrations in musculoskeletal tissues. The toxic effects of bupivacaine in bone, muscle and neural tissue, articular cartilage and the intervertebral disc in vitro were reviewed in Chapter 5. All reported effects in vitro were shown to be reversible in animal and clinical studies, with the exception of chondrotoxicity. The absence of regenerative capacity in vitro likely limits the translation of laboratory findings. Chapter 6 assesses the local toxic effects of high bupivacaine concentrations in a rat model for skeletal surgery. Rats underwent skeletal implantation of a cannula and screw, to allow bolus administration or sustained infusion of bupivacaine in three concentrations at the surgical site. Histological analysis of implant sites after 28 days did not reveal differences between bupivacaine concentrations. The third aim concerns the development of a clinically relevant hydrogel-based bupivacaine sustained release formulation for use in musculoskeletal surgery. Chapter 7 described the development and in vitro optimization of a ring-shaped hydrogel. The hydrogel displayed tunable mechanical properties and drug-releasing behavior. Drug release was sustained for 72 hours in vitro. The material was implantable, biodegradable and cytocompatible. Chapter 8 revealed that implantation of up to 8 hydrogel rings yielded sustained but low bupivacaine plasma levels, with correspondingly high surgical site levels for 72 hours. Drug release followed a first-order profile. Hydrogels elicited a mild tissue response and degraded in situ. In Chapter 9, a bridging study was performed in sheep according to Good Laboratory Practice (GLP). Sheep received either 8 pedicle screws, 8 pedicle screws combined with unloaded hydrogels, or 8 pedicle screws with bupivacaine-loaded hydrogels. Plasma bupivacaine levels remained tenfold below toxic thresholds, and were sustained for longer compared to subcutaneous infiltration of bupivacaine. Local tissue reaction and screw osseointegration were similar between groups. Taken together, the results indicate biocompatibility, biodegradability, large systemic safety margins and extended drug release of the bupivacaine-loaded hydrogels in vivo. The final aim of this thesis was to provide directions for a clinical trial, assessing safety and feasibility of the bupivacaine-loaded hydrogel for use in spine surgery. Chapter 10 presents a protocol for a phase 1B clinical trial, in which female and male adult patients with degenerative spinal disease and scheduled spine surgery are included. The patients will receive 4 or 6 hydrogels, to be co-implanted with pedicle screws. The primary outcome of the study is systemic safety of the bupivacaine hydrogel formulation as defined by the Cmax.

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Robust gelatin hydrogels for local sustained release of bupivacaine following spinal surgery

Steverink

Tol

Oosterman³

et al. 2022

Acta Biomaterialia

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Study to explore inclusion complexes of α- and β-cyclodextrin molecules with 3-octyl-1-methylimidazolium bromide with the manifestation of hydrophobic and hydrophilic interactions

Cited by 10 publications

References 42 publications

Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study

Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study

Postoperative skeletal pain

Robust gelatin hydrogels for local sustained release of bupivacaine following spinal surgery

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