Nanotransethosomes for enhanced transdermal delivery of mangiferin against rheumatoid arthritis: formulation, characterization, invivo pharmacokinetic and pharmacodynamic evaluation

Abstract

The present research study limns the preparation of MNF loaded transethosomes (MNF-TE) to improve MNF solubility, bioavailability and permeation through skin layers for transdermal delivery. MNF-TE was formulated using thin-film hydration method and optimization was done using Box-Behnken design (BBD). MNF-TEopt was characterized for Polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential and in vitro MNF release. For further evaluation, Pharmacokinetic study, Transmission electron microscopy (TEM), Skin permeation study and Confocal scanning laser microscopy (CLSM) were performed withal. The MNF-TEopt presented spherical and sealed shape vesicles with small vesicle size of 148.6 nm, entrapment efficiency of 74.23%, PDI of 0.1139 and in vitro release of 65.32%. The CLSM study unveiled that the developed formulation has greater permeation of MNF across the skin layers in comparison with the MNF suspension gel. The pharmacokinetic study demonstrated C max and AUC 0-24 h of 6.94 ± 0.51 μg/ml and 43.92 ± 7.90 μg.h/ml via transdermal route in comparison to C max and AUC 0-24 h of 3.74 ± 1.91 μg/ml and 22.96 ± 9.76 μg.h/ml presented by MNF-TE oral administration. The in vivo study revealed that the MNF-TE gel has good anti-arthritic potential in comparison with the standard diclofenac gel which was evinced by radiographic analysis and histopathological studies. Further, skin irritation study on Wistar albino rats confirm that the developed MNF-TE formulation is safer for skin application. The current investigation corroborated that the prepared TE vesicle formulation is a treasured carrier for the MNF transdermal delivery for the management of rheumatoid arthritis.

Application of QbD‐based approach to the development and validation of an RP‐HPLC method for simultaneous estimation of pregabalin and naringin in dual‐drug loaded liposomes

“…The graph shows that the medication is released rapidly during the first 5 h and then at a reduced rate over the next 24 h. This sort of releasing behaviour is optimal for improving treatment effectiveness. Initial rapid release aids in achieving therapeutic concentration but extended gradual release improves therapeutic efficacy (Adin, Gupta, Rashid, et al, 2023; Gupta, Adin, Aqil, & Mujeeb, 2023). Figure 6 depicts a chromatogram revealing the drug kinetics of PRG–NRN‐loaded nanoliposomes.…”

“…The RBF was placed in a desicator for 24 h. The dried film was hydrated in a water–PRG solution for 1 h before being stored in the refrigerator to achieve adequate swelling. The obtained dispersion was probe sonicated for 4 min with a titanium probe ultra sonicator (UP 100 H, Hielscher Ultrasonics GmbH, Berlin) and then characterized for polydispersity index (PDI), entrapment efficiency and vesicle size (Adin, Gupta, Rashid, et al, 2023; Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a; Gupta, Adin, Rashid, et al, 2023).…”

“…The RBF was placed in a desicator for 24 h. The dried film was hydrated in a water-PRG solution for 1 h before being stored in the refrigerator to achieve adequate swelling. The obtained dispersion was probe sonicated for 4 min with a titanium probe ultra sonicator (UP 100 H, Hielscher Ultrasonics GmbH, Berlin) and then characterized for polydispersity index (PDI), entrapment efficiency and vesicle size(Adin, Gupta, Rashid, et al, 2023;Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a;Gupta, Adin, Rashid, et al, 2023).2.8.2 | Characterization of prepared PRG-NRN nanoliposomesThe vesicle size and PDI of the developed PRG-NRN liposomes were estimated using a Zetasizer (Malvern Instruments, Worcestershire, UK) after diluting the sample with Mill-Q water (50 times) at 25 ± 1 C in triplicate at a scattering angle of 90 C(Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a).2.8.3 | Percentage drug entrapment efficiency and percentage drug loading The entrapment efficiency of liposomes was evaluated using ultracentrifugation. The samples were stored at 40 C overnight before being centrifuged at 20,000 rpm for 1 h at 40 C (REMI, cooling centrifuge, Mumbai, India).…”

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

“…[26][27][28][29][30] However, one limitation of transdermal drug delivery is the difficulty of drug penetration through the human skin, which is hard and resistant to infiltration. 31 The human skin comprises three main layers: the epidermis, dermis, and hypodermis. The low water concentration gradient from 75% in the viable epidermis to only 10-30% in the stratum corneum contributes to the lower permeability of molecules and drugs across the stratum corneum.…”

Application of a Quality by Design‐based approach in development and validation of an RP‐HPLC method for simultaneous estimation of methotrexate and mangiferin in dual drug‐loaded liposomes

“…Thus, our work involves the development of an economical, sensitive, robust, simple, rapid and effective HPLC method for synchronous detection of MTX and MNF utilizing the QbD approach. Validation of the developed method was done as per International Conference on Harmonization guidelines (Adin, Gupta, Ali, et al, 2022; Adin et al, 2022a, 2022b; Adin et al, 2023a, 2023b; Adin, Gupta, Aqil, et al, 2022; Adin, Gupta, Rashid, et al, 2023; Guideline IHT, 2005b; Gupta, Adin, Aqil, & Mujeeb, 2022; Gupta et al, 2023a, 2023b; Gupta, Adin, Aqil, Mujeeb, & Ahad, 2022; Gupta et al, 2022a, 2022b; Gupta, Adin, Rashid, et al, 2023). To the best of our knowledge, there is no analytical method reported for the simultaneous estimation of MTX and MNF in dual drug‐loaded nanopharmaceuticals.…”