Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In vitro optimization and in vivo evaluation

Sadarani, Bhakti; Majumdar, Anuradha; Paradkar, Shalaka; Mathur, Anupam; Sachdev, S.S.; Mohanty, Bhabani; Chaudhari, Pradip

doi:10.1016/j.biopha.2019.108770

Cited by 39 publications

(9 citation statements)

References 61 publications

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“…On the other hand, injectable formulations are invasive and also display severe hepatotoxicity and nephrotoxicity. , Whereas, intra articular injection of MTX exhibits rapid clearance of the drug from the body . Due to these adverse effects, almost 30% of the patients have to discontinue MTX therapy, while 50% of patients have to receive high doses of MTX that further increases the risk of dose-related toxicities. ,, …”

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confidence: 99%

“…9 Due to these adverse effects, almost 30% of the patients have to discontinue MTX therapy, while 50% of patients have to receive high doses of MTX that further increases the risk of dose-related toxicities. 8,10,11 To overcome the above-mentioned problems, researchers have adopted alternative routes for the delivery of MTX against RA. Previously, different lipid-based formulations of MTX had been prepared for transdermal delivery.…”

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confidence: 99%

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Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis

et al. 2020

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Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0–t , and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

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confidence: 99%

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confidence: 99%

Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis

et al. 2020

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“…Another deformable liposome was also developed to encapsulate MTX and the liposome was further loaded in a hydroxyethyl cellulose gel. The system could achieve a permeation flux of MTX to 17.37 ± 1.5 μg cm −2 h −1 in vitro (Sadarani et al, 2019), which was higher than the previous MTX–liposome–Carbopol gel (Zeb et al, 2017).…”

Section: Transdermal Delivery Of Nanomedicines For Arthritic Injuriesmentioning

confidence: 92%

Recent advances on transdermal delivery systems for the treatment of arthritic injuries: From classical treatment to nanomedicines

Shang

Younas

Zhang

2022

WIREs Nanomed Nanobiotechnol

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Arthritic injuries happen frequently during a lifetime due to accidents, sports, aging, diseases, etc. Such injuries can be cartilage/bone injuries, tendon injuries, ligament injuries, inflammation, pain, and/or synovitis. Oral and injective administration of therapeutics are typically used but cause many side effects. Transdermal administration is an alternative route for safe and efficient delivery. Transdermal formulations of non-steroidal anti-inflammatory drugs have been available on market for years and show promising efficacy in pain relieving, inflammation alleviation, infection control, and so on. Innovative transdermal patches, gels/films, and microneedles have also been widely explored as formulations to deliver therapeutics to combat arthritic injuries. However, transdermal formulations that halt disease progression and promote damage repair are translated slowly from lab bench to clinical applications. One major reason is that the skin barrier and synovial capsule barrier limit the efficacy of transdermal delivery. Recently, many nanocarriers, such as nanoparticles, nanolipids, nanoemulsions, nanocrystals, exosomes, etc., have been incorporated into transdermal formulations to advance drug delivery. The combined transdermal formulations show promising safety and efficacy.Therefore, this review will focus on stating the current development of nanomedicine-based transdermal formulations for the treatment of arthritic injuries. The advances, limitations, and future perspectives in this field will also be provided to inspire future studies and accelerate clinical translational studies.

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“…Animals were given eight Days to acclimatize to the condition and then treatment was given to the animals. [14][13] [12]This study was approved by the Animal Ethics committee of the Institute under the application number CU/2019/IAEC/02 Acute Dermal Irritation [15] [16] Acute dermal irritation was performed on the healthy rabbits. The positive control group received the treatment of the Formaldehyde in the concentration of 0.8%.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the dermal irritation and skin sensitization due to thiocolchicoside transdermal drug delivery system

Thakur

Kaur

Sharma

et al. 2022

ijhs

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The skin irritation and sensitization potential of the new transdermal patch of the Thiocolchicoside formulated with Dura 87-6908 was evaluated on the rabbits and guinea pig as per the standard guidelines of OECD. Skin irritation test was performed on the rabbits by applying the placebo patch for 72 hours and dermal reactions like edema, erythema were noted. No clinical signs or dermal reactions were observed in the rabbits. Sensitization potential was measure on the guinea pig and animal was challenged to transdermal therapeutic system of the Thiocolchicoside, negative control group while group exposed to CDNB produced the sensitization reactions. These findings proved that Thiocolchicoside does not produce any dermal toxicity, irritation and sensitization and hence it is safe for dermal use.

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Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In vitro optimization and in vivo evaluation

Cited by 39 publications

References 61 publications

Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis

Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis

Recent advances on transdermal delivery systems for the treatment of arthritic injuries: From classical treatment to nanomedicines

Evaluation of the dermal irritation and skin sensitization due to thiocolchicoside transdermal drug delivery system

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