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Nano Delivery of Antiviral Plant Bioactives as Cancer Therapeutics
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Haripriya Shanmugam, Badma Priya, Manickam Senguttuvan Swetha, Janani Semalaiyappan
Camptothecin, a quinolone alkaloid obtained from happy tree’s bark and stem (Camptotheca acuminate) is a topoisomerase I inhibitor with low aqueous solubility and instability that limits its therapeutic efficiency (Koo et al. 2006). Sterically stabilized micelles of PEGylated phospholipids with 14 nm size have been used as nanocarriers for delivering camptothecin. These PEGylated phospholipids can penetrate through the tumours that were leaky in nature. The passive targeting shows lesser concentration of drug toxicity to the healthy cells, even at higher concentration of drug to be delivered to the tumour cells (Koo et al. 2006). PDT facilitates drug nanopariculates delivery restricted to the interstitium of the tumours, and even does not enhance their intake by the cancerous cells. The cancerous cell intake happens by active directing of drug nanoparticulates by using overexpressed receptors on the cancerous cells (Bazak et al. 2014).
Nano-System as Therapeutic Means
Published in Jyoti Ranjan Rout, Rout George Kerry, Abinash Dutta, Biotechnological Advances for Microbiology, Molecular Biology, and Nanotechnology, 2022
Ananya Ghosh, Aniruddha Mukherjee
Micelles are defined as super-molecular assemblies (spherical) composed of the amphiphilic copolymer. The core of micelles is capable of housing hydrophobic compounds, and the outer shell is a hydrophilic brush-like corona which enhances its polarity, thereby allowing the delivery of contents with low solubility. 20-(S)-Camptothecin, extracted from the bark of Camptotheca acuminat e (Chinese happy tree), is a natural DNA topoisomerase 1 inhibitor, and its interference with the cytoskeleton (microtubules and actin filaments) makes it a potent agent for antineoplastic therapies. Nevertheless, its use is delimited due to low solubility, toxicity, and instability of the drug (Wang et al., 2016; Martino et al., 2017). If the surface of the micelle is further PEGylated, it escalates the ability of the nanocarrier to navigate via fenestrated vascular sites in tumors and inflamed tissue regions through passive transport, thus contributing to higher drug concentration in tumors. Several polymeric micelles containing antineoplasmic drugs, such as NK911, NK105, NC-6004, NK012, and SP1049C are under clinical trials (Oerlemans et al., 2010) while Genexol-PM (PTX), a drug with antimalignant property has been approved for usage against breast cancer (Zhang et al., 2014).
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
Camptothecin is a topoisomerase I inhibitor which has potent antineoplastic activity but has had very little clinical translation because of significant systemic toxicities. Campothecin is thus a prime candidate for nanoformulation. A drug-conjugate formulation of camptothecin and a cyclodextran-PEG polymer, marketed as CRLX-101 (formerly IT-101, Cerulean Pharma, Inc.) has shown promising preclinical and early clinical results [28–30]. There are a number of phase I/II studies utilizing CRLX-101 alone or in combination with other drugs in a number of clinical settings including RCC, NSCLC, gyn malignancies, and esophageal tumors. CRLX-101 has also been evaluated for use as a radiosensitizer with capecitabine as neoadjuvant multimodality therapy for advanced rectal cancers. A completed phase 1 study demonstrated a favorable toxicity profile, and phase II studies are ongoing.
Facile preparation of nanomicelles using polymyxin E for enhanced antitumor effects
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Xifa Lan, Quanling Guo, Zhiwei Liu, Kai Liu, Jinfeng He, Ruyu Li, Haotian Sun, Wenxiu Yao, Longgang Wang
There is an urgent demand for effective inhibition of the quick growth of tumors. To cure the tumors, many therapeutic molecules such as doxorubicin (DOX) [1], camptothecin (CPT) [2] and chlorin e6 (Ce6) [3] have been widely studied. For example, the therapeutic effect of DOX is due to the fact that DOX intercalates into DNA duplex, inhibits the synthesis of nucleic acid and induces major changes of DNA structure [4]. Ce6 can be activated by light to generate reactive oxygen species to induce the damage of cancer cells [5,6]. However, these therapeutic molecules usually have low solubility in aqueous solution and lack targeting effect in the body. These shortcomings can be relieved by construction of different kinds of drug carriers such as micelles [7,8], liposome [9], dendrimers [10,11], metal nanoparticles [12], metal-organic frameworks (MOFs) [13] and silicon nanoparticles [14]. These drug delivery carriers enhance the therapeutic effect of anticancer molecules through enhanced permeability and retention (EPR) effect to some degree. Polymer micelles are popular drug carriers with many kinds of structures [15]. Many synthetic polymers such as polyethylene glycol, poly(N-isopropylacrylamide), polycaprolactone and poly(lactic-co-glycolic acid) have been used to construct various kinds of polymer micelles [16–18]. However, many synthetic polymers suffer from the disadvantages of complex synthetic process and wide distribution of molecular weights [19,20].
Camptothecin prodrug nanomicelle based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Ya Gao, Yi Xiao, Shiyuan Liu, Jiahui Yu
Camptothecin (CPT), isolated originally from Camptotheca acuminate, first identified in the mid-60s by Wall and Wani [30] has promising anticancer effects. It can inhibit topoisomerase I to induce apoptosis in rapidly dividing tumor cells [31,32]. Unfortunately, the drug has been prevented from being approved due to its poor solubility and unpredictable side effects [33]. It has been confirmed that the severe toxicity of CPT mainly results from its carboxylate form [34]. As well known, CPT exists in two forms depending on pH values [35]. The first one is closed lactone ring (E-ring) form at pH below 5, which is essential to the treatment of cancer. The second one is ring-open carboxylate form at basic pH. The 20-OH of E-ring can accelerate hydrolysis of CPT, resulting in ring opening at physiological pH. At the same time, human serum albumin can bind preferentially with the carboxylate form, which will result in the lactone ring opening more rapidly [36,37]. However, it has been found that modifying CPT at the 20 position as ester to construct prodrugs of CPT stabilizes the active lactone ring under physiological conditions [38]. Nowadays, CPT has been conjugated to a variety of polymers to form macromolecule polymer prodrugs of CPT, such as polyethylene glycol [39,40], dextran [41] and poly (L-glutamic acid) [42].
Valuable alkaloids content is preserved in Camptotheca acuminata and Morus alba grown in trace elements contaminated soil
Published in International Journal of Phytoremediation, 2022
Julien Lamontagne, Eszter Sas, Gilles Vincent, Kankan Shang, Frédéric E. Pitre, Michel Labrecque
Wood phytochemicals include alkaloids, a broad and diverse group of nitrogen-containing molecules that are specific to genera or few species (Desgagné-Penix 2017). Alkaloids comprise very potent modulators of biological activities, like caffeine and quinine (Desgagné-Penix 2017). Less known alkaloids are the alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ), found in Morus alba, and the type I topoisomerase inhibitor camptothecin (CPT), isolated from Camptotheca acuminata. The former has antidiabetic properties (Desgagné-Penix 2017), while the latter is used in the synthesis of an anticancer drug (Isah 2016).