Integrative Nanomedicine for New Therapies by Anand Krishnan & Anil Chuturgoon

Author:Anand Krishnan & Anil Chuturgoon
Language: eng
Format: epub
ISBN: 9783030362607
Publisher: Springer International Publishing

3.6 Polymeric Micelles as Polymeric Nanoparticles and Their Applications in Drug Delivery

Despite of the development achieved in drug delivery, designing an appropriate carrier to deliver drugs with low aqueous solubility is still challenging. Micelles formed of surfactants have been used to solubilize drugs with low aqueous solubility. But, these surfactants are suffering from the high critical micelle concentration and the related low stability. Therefore, polymeric micelles were developed presenting higher stability in blood stream and higher tolerability. In addition to their low toxicity and high loading capacity, they provide controlled drug release and prolonged therapeutic potential (Ahmad et al. 2014). When polymeric micelles are present in water, their hydrophobic moiety is excluded from water. Polymeric nanoparticles possess a special core shell structure where hydrophobic part encapsulates hydrophobic agents, proteins or DNA. The hydrophilic moiety of polymeric micelles has an interesting role because of its brush like structure that permits the hydrophilic moiety to keep the hydrophobic moiety safe from biological invasions. Additionally, proteins adsorption on micelles could be minimized by the hydrophilic shell (Ahmad et al. 2014; Cho et al. 2014). Polymeric micelles are formed by dispersing a block copolymer having hydrophobic and hydrophilic moieties. In addition, cross linking the core of micelle can enhance its stability. Polyethylene glycol PEG is widely used to provide a stealth character as a hydrophilic shell. Polymeric micelles possess a passive targeting to tumor cells due the low lymphatic drainage to tumor cells and the high tumor vascularization resulting in an enhanced penetration and retention (EPR) effect of the micelles (Englert et al. 2018).

Due to polymeric micelles features they are considered as potential candidates to treat cancer. Many anti-tumor drugs such as Genexol®‐PM, NK105 and SP1049C were studied in clinical trials (Banik et al. 2016). Genexol-PM is paclitaxel loaded polymeric micelle having the approval in South Korea to treat non-small cell lung cancer and breast cancer. Its main components are paclitaxel and low molecular weight amphiphilic diblock copolymer, monomethoxy poly (ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA). Genexol-PM have been shown to possess higher tolerability compared to Taxol and mush lower toxicity. The tolerated dose of Genexol-PM is two to three times that of taxol. The size of the polymeric micelle is approximately 24 nm (Fig. 17a) and its zeta potential is almost −8 mV. Paclitaxel is released in a first-order release kinetic (Fig. 17b). In vivo experiments showed that Genexol-PM is more efficacious as radiosensitizer compared to taxol. Additionally, after 6 h of administration, it was proved that Genexol-PM gave mush lower exposure of paclitaxel to normal lung cells than taxol (Werner et al. 2013).

Fig. 17a Transmission electron microscopy image of Genexol-PM showing a monodispersed population of particles with a narrow size distribution of 23.0 ± 4.5. b Drug-release curve of Genexol-PM. Genexol-PM releases paclitaxel (Ptxl) in a first-order release kinetic. Genexol-PM was incubated in phosphate buffered saline at 37 °C. From Werner et al. (2013) with permition

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