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Recent Progress in Polymer Therapeutics as Nanomedicines
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Sahar Israeli Dangoor, Shani Koshrovski Michael, Hemda Baabur-Cohen, Liora Omer, Ronit Satchi-Fainaro
Paclitaxel is a very potent cytotoxic drug commonly used for the treatment of advanced breast and ovarian cancers and a wide range of other solid tumors [143]. However, it is hydrophobic and causes side effects such as neutropenia, neuropathies, and hypersensitivity (due to the solubilizing Cremophor EL) [144, 145]. In order to improve its safety profile, paclitaxel was conjugated with high loading to PGA (paclitaxel poliglumex, OpaxioTM; CTI BioPharma Corp.). Although paclitaxel is conjugated to PGA via an ester bond, the polymer backbone is generally stable in the circulation [143, 146]. Opaxio was evaluated in several phase III clinical trials, in which it failed to show superiority in overall survival in non-small-cell lung cancer patients [143]. Opaxio is currently being evaluated in a phase III clinical trial against advanced ovarian, primary peritoneal or fallopian tube cancer [143, 147].
Bioengineering Approach on Terpenoids Production
Published in Dijendra Nath Roy, Terpenoids Against Human Diseases, 2019
Production of various diterpenoids in microbial system has also been reported. Paclitaxel is one of the most commonly used anti-cancer drugs. Production of paclitaxel and its intermediates in microbes is a highly active research area. E. coli does not typically contain the GGPP synthase enzyme, so the heterologous codon-optimized GGPPS is used. By using a multivariate modular approach, the upstream native MEP pathway and downstream heterologous diterpenoid pathway was engineered in E. coli and an increase of ∼15,000-fold of taxadiene was observed when compared to other previous studies. Further, a CYP, taxadiene 5α-hydroxylase gene was introduced into the strain to generate taxadiene 5α-ol, a precursor of paclitaxel immediately following taxadiene (Ajikumar et al. 2010). Engineering efforts for taxadiene production in yeast did not yield high titres. Engels et al. (2008) reported 8.7 mg/L of taxadiene, in S. serevisiae by expressing the plant Taxus chinensis taxadiene synthase, truncated HMGR genes and an archaeal (Sulfolobus acidocaldarius) GGPPS gene (Engels et al. 2008).
Potential Use of Bioactive Compounds from Waste in the pharmaceutical Industry
Published in Quan V. Vuong, Utilisation of Bioactive Compounds from Agricultural and Food Waste, 2017
According to the World Health Organization, a great number of people still rely on plant-based traditional medicines for primary health care. The most widely used breast cancer drug is paclitaxel (Taxol®), isolated from the bark of Taxus brevifolia. Since the bark from about three mature 100-year old trees is required to provide 2 grams of the drug for a course of treatment, paclitaxel is now produced synthetically (Purvis 2000, Dewick 2002). Baccatin III is present in much higher quantities in the needles of T. brevifolia. Another antitumor molecule is ingenol 3-O-angelate, which is derived from a compound isolated from the sap of Euphorbia peplus. Calanolides from the Calonphyllum species gave results in the treatments of AIDS. Artemisinin, isolated from the plant Artemisia annua, is an approved antimalarial drug (Colegate and Molyneux 2008). Grandisines A and B are two indole alkaloids isolated from the leaves of the Australian rainforest tree, Elaeocarpus grandis, for use as analgesic agents (Carroll et al. 2005). Apomorphine is a derivative of morphine which is isolated from the poppy (Papaver somniferum) and is used to treat Parkinson’s disease (Deleu et al. 2004).
3D collagen porous scaffold carrying PLGA-PTX/SDF-1α recruits and promotes neural stem cell differentiation for spinal cord injury repair
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Zhixiang Li, Panpan Xu, Lijun Shang, Bingxu Ma, Huihui Zhang, Liangmin Fu, Yuanyuan Ou, Yingji Mao
The promotion of central neurogenesis requires certain biological signals more than anything else. Microtubule abnormalities have been reported in some nervous system degenerative diseases, such as Parkinson’s and Alzheimer’s. Hence, the use of microtubule stabilizers is a promising strategy for CNS generation. For SCI, axonal microtubule stability is crucial to ensure the growth of damaged axons. Paclitaxel, an anticancer drug, is often used in clinical tumor research because of its ability to interfere with cell division and affect the cell cycle. In the present study, the effects of different PTX concentrations on NSCs differentiation were investigated. Under normal physiological conditions, 10 ng/mL PLGA-PTX was more favorable for NSCs differentiation. The differentiation rate of neurons showed an initial trend of increase followed by a decrease, and higher doses of PTX had an inhibitory effect on neuronal differentiation. Recent studies have shown that low PTX doses not only exert a direct intrinsic effect on the neuronal differentiation of NSCs but also reverse the inhibitory effects of myelin proteins on neuronal axon growth [11]. In addition to microtubule stabilizers, some neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3), play prominent roles in SCI repair [55, 56]. They are both able to enhance the neuronal differentiation of NSCs and provide another viable strategy.