Efficacy of targeted liposomes and nanocochleates containing imatinib plus dexketoprofen against fibrosarcoma

Abstract

The main challenges in treating cancer using chemotherapeutics are insufficient dose at the target site and the development of drug resistance, while higher doses can induce side effects by damaging nontarget tissues. Combinatorial drug therapy may overcome these limitations by permitting lower doses and more specific targeting, thereby mitigating drug resistance and nontarget side effects. Recent reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer potential and can be used together with conventional chemotherapeutics to improve efficacy and safety. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as model drugs to develop targeted surface-modified liposome and nanocochleate formulations for fibrosarcoma treatment. The physicochemical properties and in vitro efficacy of various formulations were evaluated by measurement of particle size distribution, polydispersity index, zeta potential, encapsulation efficiency, diffusion through Caco-2 cells, and toxicity in culture. Selected formulations were then evaluated in fibrosarcoma-bearing model mice by histopathological observations and tyrosine kinase receptor inhibition assays.The most effective formulation on the fibrosarcoma model was a PEGylated nanocochleate formulation. These findings provide a foundation for developing more effective formulations and chemotherapeutic strategies for the treatment of fibrosarcoma and other types of cancer.

New uses of ketoprofen – a review of studies from 2015 to 2021

“…In recent years, several studies have been published suggesting the chemopreventive potential of K [14,[21][22][23][24]. In several diverse types of tumors, researchers found enhanced COX-2 expression.…”

“…In 2019, Çoban et al developed a PEGylated nanocochleate formulation containing imatinib and dexketoprofen (IMA-DEX PEG COH) against fibrosarcoma. They also synthesized three similar drugs that were not as effective [23]. In this study, a mouse fibrosarcoma model was used and tumor size, histopathology and tyrosine kinase receptor inhibition were assessed after 14 days of treatment with the new drug.…”

NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future

“…Interestingly, these nanocarriers demonstrated synergistic effects in cancer therapy and reduced their gastric side effects. Some important formulation approaches with NSAIDs or NSAID derivatives alone and combined with chemotherapeutic agents are micelles, − nanomicelles, − liposomes, , transferrin-bearing vesicles, nanoparticles, ,− PEGylated nanocochleate, nanoexosomes, , cyclodextrins, and poloxamers (Table ).…”

“…However, as has already been discussed herein, some of these NSAID derivatives have limited metabolic stability due to their rapid hydrolysis by carboxylesterases at their carboxylic ester link. In this context, several formulations encapsulating these analogs have been developed to improve their bioavailability and efficacy ,,,− and are summarized in Table . We think that these formulations could render interesting options in terms of delivering releasing-NSAIDs by providing a more controlled release of the therapeutic drug.…”

Extended Release of DTPA via Encapsulation into Nanoparticles for the Decorporation of Deposited Radioactive Contaminants in the Lungs

“…Liposomes have been used as carriers to facilitate the processing of various bioactive molecules in food, cosmetic, pharmaceutical, and farming products [187,188,189,190,191,192]. Encapsulating drugs in liposomes has proven to be a promising technique in drug delivery due to their biocompatibility, biodegradability, and non-immunogenicity for systemic and nonsystemic administrations [ 193,194,195,196]. In therapeutic medicines, liposomes can protect the encapsulated drug from decomposition by enzymes, bile salts, intestinal flora, and free radicals in the human body [197,198].…”