Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat

Italiya, Kishan S.; Singh, Arihant Kumar; Mittal, Anupama

doi:10.1208/s12249-021-01980-5

Cited by 7 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors have cited additional references within the Supporting Information. [33][34][35][36][37][38][39][40][41][42]…”

Section: Supporting Informationmentioning

confidence: 99%

Electrochemical Synthesis of Added Valuable Purine Alkaloid Metabolites from Caffeine Feedstock Employing a Structure Electro-Activity Relationship (SeAR) Approach

Asra,

Jones

2024

Preprint

View full text Add to dashboard Cite

The development of electrochemical approaches to the valorization of abundant natural products into high value medications and metabolites is of pharmaceutical interest. In this study, we explored the electrosynthetic behavior of the abundant legal psychoactive, caffeine, a representative member of the purine alkaloid class. Initial screening of the cyclic voltammetric behavior of eleven exemplar purine alkaloids revealed a predicted structure electroactivity relationship (SeAr). Optimization of the current controlled electrochemical (CCE) reaction informed by cyclic voltammetry measurements enabled the dialing-in/out of differential oxidative metabolic products. Sequential desmethylation around the purine ring was observed both by isolation and comparison of reference standards using HPLC. Amide, imide, and a novel N-methyl heteroaryl oxidation mechanism are observed. Tractable quantities of the high-value theophylline (medication) and paraxanthine (dietary supplement) were isolated in 17% and 8% b.r.s.m. employing an electrolyte recovery strategy. This approach offers a marked improvement compared to other approaches (chemical 0.8% and enzymatic 0.97% yields) and may have potential in other natural product and drug discovery settings.

show abstract

“…The authors have cited additional references within the Supporting Information. [33][34][35][36][37][38][39][40][41][42]…”

Section: Supporting Informationmentioning

confidence: 99%

Electrochemical Synthesis of Added Valuable Purine Alkaloid Metabolites from Caffeine Feedstock Employing a Structure Electro-Activity Relationship (SeAR) Approach

Asra,

Jones

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…41 After 48 h, 3-[4,5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was performed and the inhibition in cell growth was determined with respect to untreated cells (media only). 42 = × %cell viability absorbance absorbance 100 sample wells untreated wells (5) Once the cell compatibility was confirmed, freshly seeded MIN-6 cells (5000 cells/well) were further exposed to the above-mentioned mixture of proinflammatory cytokines to induce inflammation 43 followed by treatment with free LSF and synthesized LSF prodrugs (∼20 μM free LSF). After 48 h, cell viability was analyzed by MTT assay recording absorbance at 560 and 630 nm followed by calculating the % cell viability using eq 5.…”

Section: ■ Experimental Designmentioning

confidence: 99%

“…The cells incubated in growth media only served as the negative control, while the cells incubated with a cocktail of three different proinflammatory cytokines (TNF-α; 10 ng/mL, IL-1β; 5 ng/mL and IFN-γ; 100 ng/mL) served as the positive control . After 48 h, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was performed and the inhibition in cell growth was determined with respect to untreated cells (media only) Once the cell compatibility was confirmed, freshly seeded MIN-6 cells (5000 cells/well) were further exposed to the above-mentioned mixture of proinflammatory cytokines to induce inflammation followed by treatment with free LSF and synthesized LSF prodrugs (∼20 μM free LSF).…”

Section: Experimental Designmentioning

confidence: 99%

Role of Chain Length and Degree of Unsaturation of Fatty Acids in the Physicochemical and Pharmacological Behavior of Drug–Fatty Acid Conjugates in Diabetes

et al. 2021

Self Cite

View full text Add to dashboard Cite

Several drug–fatty acid (FA) prodrugs have been reported to exhibit desirable physicochemical and pharmacological profile; however, comparative beneficial effects rendered by different FAs have not been explored. In the present study, four different FAs (linoleic acid, oleic acid, palmitic acid, and α-lipoic acid) were selected based on their chain length and degree of unsaturation and conjugated to Lisofylline (LSF), an antidiabetic molecule to obtain different drug–FA prodrugs and characterized for molecular weight, hydrophobicity, purity, self-assembly, and efficacy in vitro and in vivo in type 1 diabetes model. Prodrugs demonstrated a 2- to 6-fold increase in the plasma half-life of LSF. Diabetic animals treated with prodrugs, once daily for 5 weeks, maintained a steady fasting blood glucose level with a significant increase in insulin level, considerable restoration of biochemical parameters, and preserved β-cells integrity. Among the different LSF-FA prodrugs, LSF-OA and LSF-PA demonstrated the most favorable physicochemical, systemic pharmacokinetic, and pharmacodynamic profiles.

show abstract

Targeting IL-12 family cytokines: A potential strategy for type 1 and type 2 diabetes mellitus

Luo,

Ning,

et al. 2024

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat

Cited by 7 publications

References 48 publications

Electrochemical Synthesis of Added Valuable Purine Alkaloid Metabolites from Caffeine Feedstock Employing a Structure Electro-Activity Relationship (SeAR) Approach

Electrochemical Synthesis of Added Valuable Purine Alkaloid Metabolites from Caffeine Feedstock Employing a Structure Electro-Activity Relationship (SeAR) Approach

Role of Chain Length and Degree of Unsaturation of Fatty Acids in the Physicochemical and Pharmacological Behavior of Drug–Fatty Acid Conjugates in Diabetes

Targeting IL-12 family cytokines: A potential strategy for type 1 and type 2 diabetes mellitus

Contact Info

Product

Resources

About