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Formulation and in vitro evaluation of quercetin loaded carbon nanotubes for Cancer Targeting

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International Research Journal of Engineering and Technology (IRJET)

e-ISSN: 2395-0056

Volume: 10 Issue: 06 | Jun 2023

p-ISSN: 2395-0072

www.irjet.net

Formulation and in vitro evaluation of quercetin loaded carbon nanotubes for Cancer Targeting Zahra Alimohammadi1, Asma Zamansani2, Azadeh Abreshteh3, Mehrsa Edalaat4, Zohreh Ebrahimi5 1Faculty of Chemical Engineering, Naghshe Jahan University, Isfahan 8199874941, Iran; 2 Faculty of Chemical Engineering, Naghshe Jahan University, Isfahan 8199874941, Iran 3 Faculty of Chemical Engineering, Naghshe Jahan University, Isfahan 8199874941, Iran 4Faculty of Chemical Engineering, Naghshe Jahan University, Isfahan 8199874941, Iran 5Faculty of Chemical Engineering, Naghshe Jahan University, Isfahan 8199874941, Iran

---------------------------------------------------------------------***--------------------------------------------------------------------One way to overcome these drawbacks is to entrap/adsorb Abstract - Quercetin has high level antioxidant and antiradical properties that are considered beneficial to cancer treatment. However, therapeutic applications of quercetin have been restricted due to its limited solubility and instability in physiological medium. The purpose of this study was to develop quercetin – Loaded carbon nanotube and to evaluate the potential of the carrier as a topical delivery system in cancer therapy. The drug delivery system has been designed based on functionalized carbon nanotubes by chitosan. Then, quercetin was conjugated to the carrier. The highest loading efficiency (38%) was achieved at 4oC and equal initial weight ratio of drug/carrier. The drug delivery system is stable under neutral pH conditions (pH 7.4), while effectively released quercetin at reduced pH conditions (pH 5.5). In vitro cytotoxicity assays showed that functionalized carbon nanotube did not exhibit notable toxicity against Hela cells; whereas, the cytotoxicity of quercetin conjugated carrier increased significantly in comparison with pure quercetin. Hence, such a targeting nanocarrier is a suitable candidate for targeted drug delivery in tumor therapy.

this molecule into carriers. Since nanoscale drug delivery carriers offer potential advantages, which include enhancement of quercetin solubility and bioavailability, improved tissue macrophages distribution, enhancement of pharmacological activity, sustained delivery, and protection from physical and chemical degradation [9,10], a number of carriers such as liposomes [11,12,13], lipids [14,15,16], micelles [17, 18], polymeric nanoparticles [19, 20], magnetic nanoparticles [21, 22] and graphene [23] have been applied for entrapment of quercetin. Recently, single walled carbon nanotubes (SWNTs) have been applied for targeting delivery of various anti-cancer drugs such as doxorubicin and paclitaxel [1, 24]. Since single walled carbon nanotubes (SWNT) provide unique properties such as high surface area (1300 m2/gr) allowing for higher drug loading and possibility for accompanying additional therapeutic ligands through surface functionalization, recently they have attracted many attentions in the treatment and diagnosis of cancer.

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However, drug delivery systems based on SWNTs still face critical challenges. They are potentially toxic and extremely hydrophobic. Functionalization of carbon nanotubes by covalent and non-covalent interactions can improve their compatibility and cellular uptake, decrease their hydrophobicity, and, make them nontoxic. Surfactants [27], peptides and polymers [1,28] have been used to modify SWNT via non covalent interactions. Among the frequently used biological species, chitosan is much more attractive due to its biodegradability and biocompatibility which can endow the SWNTs excellent water solubility and good biological compatibility [29,30]. Moreover, presence of amine group in chitosan structure can facilitate attachment of targeting ligands to the drug delivery system [31,32]. In this paper, for the first time, to the best our knowledge, single walled carbon nanotube was used to targeting delivery of quercetin. Chitosan have been applied to functionalization of carbon nanotubes. First, the influence of the binding conditions during the drug loading step (e.g., temperature, initial weight ratio of drug/carrier and initial amount of chitosan applied for functionalization) on the drug

Carbon nanotube, Quercetin, Chitosan, targeting, Drug delivery, Cancer therapy

1.INTRODUCTION Cancer is one of the main causes of death in the world and its victims increase every day [1]. Quercetin (3, 3´, 4´, 5´-7penta-hydroxy flavone) (fig1) is one of the most abundant flavonoids in plants found in fruits, vegetables and herbs [2]. It has a broad extent of chemotherapeutic properties for many diseases such as anti-cancer, anti-inflammatory, antiviral, antiradical and anti-oxidant [3, 4]. However, its superior anti-cancer activity is well demonstrated in colon, breast, ovarian and lung cancer cells [5,6]. In vivo reversal efficacy of quercetin is not satisfactory when it is administered systemically via free drug due to its low solubility in aqueous media (7.7 µg/mL in water), poor permeability, low bioavailability (about 1% in men) [7], biodegradation limits and high binding ratio of drug–plasma protein (99.4%) [8].

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