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

Abstract

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.

Preparation and properties of triethyl citrate plasticized chitosan‐based membranes for efficient release of curcumin

“…As the amount of TEC increases, the water solubility of the CS/SS‐Cur first increases and then decreases. This may be because with the addition of TEC, the interaction with starch and chitosan macromolecules increases the molecular distance, which weakens the interaction between chitosan and starch macromolecules, and the formed structure becomes loose so that water molecules can easily enter, indicating the ability of TEC to improve the solvation of polymeric chains 41 . However, with the addition of TEC, a strong and rigid structure is formed in the polymer chain, excess TEC cannot combine with polymer molecules and then reduces the water solubility of the membrane as ester compound.…”

Polysaccharide-Based Transdermal Drug Delivery

“…Polymeric films have attracted interest as an alternative to patches because they are transparent, flexible, non-occlusive, and easy to administer while prolonging the drug retention time in the skin [ 79 ]. The films demonstrate greater drug loading and better drug release than ointment [ 80 ]. The film-forming ability of polysaccharides and their unique adhesion properties have attracted widespread attention.…”

Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives

“…Thus, swelling is an important property of chitosan membranes, especially those for oral use [ 84 ]. The addition of hydrophobic compounds reduces the swelling of polysaccharide membranes [ 85 ], whereas various hydrophilic compounds such as hydroxypropyl β-cyclodextrin (HPβCD) and triethanolamine improve the solvation of polymer chains and increase swelling [ 62 , 86 ].…”