Inclusion complexation and liposomal encapsulation of an isoniazid hydrazone derivative in cyclodextrin for pH-dependent controlled release
- Safari, Justin B, Mona, Lamine B, Sekaleli, Bafokeng T, Avudi, Bénite K, Isamura, Bienfait K, Mukubwa, Grady K, Salami, Sodeeq A, Mbinze, Jérémie K, Lobb, Kevin A, Krause, Rui W M, Nkanga, Christian I
- Authors: Safari, Justin B , Mona, Lamine B , Sekaleli, Bafokeng T , Avudi, Bénite K , Isamura, Bienfait K , Mukubwa, Grady K , Salami, Sodeeq A , Mbinze, Jérémie K , Lobb, Kevin A , Krause, Rui W M , Nkanga, Christian I
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452727 , vital:75166 , xlink:href="https://doi.org/10.1016/j.jddst.2023.104302"
- Description: Tuberculosis, a predominantly pulmonary pathology, is currently the deadliest infection worldwide. Its treatment is based on combination therapy involving selected antimicrobials including Isoniazid. However, physicochemical properties of isoniazid negatively affect the clinical performance of current tuberculosis regimens, causing drug resistance development and increasing mortality rates. Liposomal encapsulation improves antituberculosis drug delivery; however, nano-formulation of isoniazid remains challenging due to its small molecular size and high hydrophilicity. Therefore, this study aimed to derivatize isoniazid and formulate a controlled delivery system using the concept of drug-in-cyclodextrins-in-liposomes to enhance drug biopharmaceutical properties. A prodrug of isoniazid was synthesized and screened for its ability to form stable complexes with α, β, and γ cyclodextrins. A selected inclusion complex with β-cyclodextrin was encapsulated in liposomes and assessed for controlled release of isoniazid. Successful formation of a 1:1 complex was established and characterized, followed by molecular modeling studies to demonstrate strength of the interactions within the complex and predicted complex structure. The inclusion complex was successfully encapsulated in liposomes using the thin film hydration method and the ethanol injection ultrasonic dispersion, with the latter giving the best results. These findings demonstrate the potential.
- Full Text:
- Date Issued: 2023
- Authors: Safari, Justin B , Mona, Lamine B , Sekaleli, Bafokeng T , Avudi, Bénite K , Isamura, Bienfait K , Mukubwa, Grady K , Salami, Sodeeq A , Mbinze, Jérémie K , Lobb, Kevin A , Krause, Rui W M , Nkanga, Christian I
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452727 , vital:75166 , xlink:href="https://doi.org/10.1016/j.jddst.2023.104302"
- Description: Tuberculosis, a predominantly pulmonary pathology, is currently the deadliest infection worldwide. Its treatment is based on combination therapy involving selected antimicrobials including Isoniazid. However, physicochemical properties of isoniazid negatively affect the clinical performance of current tuberculosis regimens, causing drug resistance development and increasing mortality rates. Liposomal encapsulation improves antituberculosis drug delivery; however, nano-formulation of isoniazid remains challenging due to its small molecular size and high hydrophilicity. Therefore, this study aimed to derivatize isoniazid and formulate a controlled delivery system using the concept of drug-in-cyclodextrins-in-liposomes to enhance drug biopharmaceutical properties. A prodrug of isoniazid was synthesized and screened for its ability to form stable complexes with α, β, and γ cyclodextrins. A selected inclusion complex with β-cyclodextrin was encapsulated in liposomes and assessed for controlled release of isoniazid. Successful formation of a 1:1 complex was established and characterized, followed by molecular modeling studies to demonstrate strength of the interactions within the complex and predicted complex structure. The inclusion complex was successfully encapsulated in liposomes using the thin film hydration method and the ethanol injection ultrasonic dispersion, with the latter giving the best results. These findings demonstrate the potential.
- Full Text:
- Date Issued: 2023
Unveiling the reactivity of truxillic and truxinic acids (TXAs): deprotonation, anion center dot center dot center dot HO, cation center dot center dot center dot O and cation center dot center dot center dot pi interactions in TXA (0) center dot center dot center dot Y+ and TXA (0) center dot center dot center dot Z (-) complexes (Y= Li, Na, K; Z= F, Cl, Br)
- Isamura, Bienfait K, Patouossa, Issofa, Muya, Jules T, Lobb, Kevin A
- Authors: Isamura, Bienfait K , Patouossa, Issofa , Muya, Jules T , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452827 , vital:75173 , xlink:href="https://link.springer.com/content/pdf/10.1007/s11224-022-01965-5.pdf"
- Description: Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA0 , and Y+ (Y=Li, Na, K) and Z− (Z=F, Cl, Br) ions using M06-2X, B3LYP and 휔 B97XD functionals in conjunction with the 6–31+ +G(d,p), aug-cc-pVDZ(-X2C) and 6–311+ +G (d, p) basis sets. Our computations suggest that Y+ cations can bind to TXA0 through several combinations of cation…O and cation-π interactions, while Z− anions generally establish anion… H–O contacts. Predicted binding energies at the M06-2X/6–311+ +G(d,p) level range between−26.6 and−70.2 kcal/mol for cationic complexes and−20.4 and−62.3 kcal/mol for anionic ones. As such, TXA0 appears as an amphoteric molecule with a slight preference for electrophilic (cation... O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA0 . Anions do not behave uniformly towards TXA0 : while the fuoride anion F− induces the deprotonation of TXA0 , Br− and Cl− do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA0 …Y+ and TXA0 …Z− complexes are mainly stabilized by electrostatic and inductive efects, whose combined contributions account for more than 60 percent of the total interaction energy.
- Full Text:
- Date Issued: 2023
- Authors: Isamura, Bienfait K , Patouossa, Issofa , Muya, Jules T , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452827 , vital:75173 , xlink:href="https://link.springer.com/content/pdf/10.1007/s11224-022-01965-5.pdf"
- Description: Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA0 , and Y+ (Y=Li, Na, K) and Z− (Z=F, Cl, Br) ions using M06-2X, B3LYP and 휔 B97XD functionals in conjunction with the 6–31+ +G(d,p), aug-cc-pVDZ(-X2C) and 6–311+ +G (d, p) basis sets. Our computations suggest that Y+ cations can bind to TXA0 through several combinations of cation…O and cation-π interactions, while Z− anions generally establish anion… H–O contacts. Predicted binding energies at the M06-2X/6–311+ +G(d,p) level range between−26.6 and−70.2 kcal/mol for cationic complexes and−20.4 and−62.3 kcal/mol for anionic ones. As such, TXA0 appears as an amphoteric molecule with a slight preference for electrophilic (cation... O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA0 . Anions do not behave uniformly towards TXA0 : while the fuoride anion F− induces the deprotonation of TXA0 , Br− and Cl− do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA0 …Y+ and TXA0 …Z− complexes are mainly stabilized by electrostatic and inductive efects, whose combined contributions account for more than 60 percent of the total interaction energy.
- Full Text:
- Date Issued: 2023
- «
- ‹
- 1
- ›
- »