Analytical Method for Transdermal Delivery of the Anti-angiogenic Compound TNP-470

Abramov, Eva; Schwob, Ouri; Benny, Ofra

doi:10.4172/2155-9872.1000365

Cited by 1 publication

(7 citation statements)

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“…We previously showed the potential of TNP‐470 to penetrate through the skin. We established a reliable analytical method for detecting the drug in Franz assay through porcine skin and showed that 25 % (w/w) of the initial applied drug was penetrating across the skin after 72 hours . In light of the fact that the skin's protective function provides an outstanding transdermal barrier that limits the penetration of drugs throw the skin, these high percentage of penetration suggesting that TNP‐470 is an excellent candidate for transdermal drug delivery.…”

Section: Discussionmentioning

confidence: 99%

“…However, we decided to continue with PEG 400 because of stability consideration, since glycerol is a small molecule and might migrate away and destabilize the matrix. Stability of TNP‐470 in the film was achieved by maintaining the pH of the mixture before casting in the range of TNP‐470 stability, 5.0 …”

Section: Discussionmentioning

confidence: 99%

“…To compare the permeation rates from both dermal formulations, film and ointment, with permeated rates from TNP‐470 solution, which were calculated in our previous study, we found that after 24 hours, 14 wt% of TNP‐470 permeated through the pig skin from the solution compared with only 2% from the ointment and 3% from the film. This fact was expected because drug absorption and further penetration into the skin membrane is a multistep process, starting by an initial release of drug from the vehicle, dissolution of the drug, subsequent adsorption, and penetration.…”

Section: Discussionmentioning

confidence: 99%

“…HPLC determination assay in stable conditions was developed and presented in detail in our previous study . Simple chromatographic conditions were achieved by using Shimadzu model LC‐20 instrument with photodiode array (PDA) detector.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, we presented an analytical method to detect free TNP‐470 permeability through pig skin using Franz diffusion cells method. We demonstrated excellent permeability properties of TNP‐470 solution of 1250 μg/cm 2 after 72 hours,, which was 25% w/w from the initial amount . The broad stability and degradation study of TNP‐470 and identification of optimized mediums and conditions to stabilize it provided the basis that enabled to develop formulations that are presented here.…”

Section: Introductionmentioning

confidence: 99%

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Film‐ and ointment‐based delivery systems for the transdermal delivery of TNP‐470

Abramov

Schwob

Benny

2019

Polymers for Advanced Techs

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Pathological angiogenesis, the process of new blood vessel formation, is responsible for a broad range of neovascular‐related systemic diseases. One of the first antiangiogenic compounds tested in clinical trials against cancer was TNP‐470. Despite promising activity the injectable drug showed poor plasma stability and caused adverse side effects in high doses lead to termination of the trials. In our current work, we introduce the development of a transdermal delivery systems for controlled release of TNP‐470. Such formulation can potentially reduce toxicity due to controlled continuous dosing and improve stability by avoiding gastrointestinal first pass metabolism. Although transdermal delivery is a very challenging route for drug administration due to the low permeability of the skin, here we present a successful development of two different drug delivery systems, film and ointment for dermal application of TNP‐470. Chitosan film had high loading capacity of up to 50% w/w of TNP‐470 compared with 10% maximum loading in hydrocarbon ointment. A detailed step‐by‐step development of TNP‐470 films, from the initial solvent screening to final optimized formulation, is presented. Ex vivo skin permeation studies demonstrated a superior release of the drug from the film formulation compared with the ointment. Furthermore, histological test of the skin confirmed ointment safety showing no evidence of skin tissues damage. Our results present novel, promising, controlled release drug delivery systems with improved stability, efficacy, and safety profile of TNP‐470 via transdermal route.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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