Polymeric Micelles: A Novel Approach towards Nano-Drug Delivery System

Nano delivery systems, polymeric micelles represent one of the most promising delivery platforms for therapeutic compounds. It has shown that a poorly soluble molecule which has high potency and remarkable toxicity can be encapsulated with the polymeric micelle. There are various poorly soluble drugs used in micellar preparations, mostly for their anti-cancer activity. Drugs in the inner core protect the drug from degradation and allow drug accumulation in the tumour site in the case of cancer treatment. Block copolymers are chosen based on the physicochemical characteristics of medicinal drugs. The amphiphilic block copolymer structure has both lipophilic and hydrophilic blocks, which enclose tiny hydrophobic molecules. It is a targeted drug delivery method because of its high effectiveness for drug retention in tissue, prevention of enzymes from degradation, and improvement of the cellular absorption mechanism. In an experimental environment, variations in temperature and solvent polarity stimulate copolymer micelle self-assembly. This is a thermodynamically guided procedure in which self-assembly happens by converting polymeric micelles. These aggregates go from a non-equilibrium to a thermodynamically equilibrium state, and they stay stable for a long time. The balance of thermodynamic and kinetic forces is critical in micelles self-assembly because the kinetic process predicts assembly behaviour and hierarchical structure. The purpose of this special issue is to provide an updated overview of micelles, a number of polymers and drugs commonly used in micellar preparation and their application.

Designing Highly Stable Poly(sarcosine)-based Telodendrimer Micelles with High Drug Content Exemplified with Fulvestrant

Polymeric micelles have been extensively used as nanocarriers for the delivery of chemotherapeutic agents aiming to improve their efficacy in cancer treatment. However, poor loading capacity, premature drug release, non-uniformity and reproducibility still remain the major challenges. To create a stable polymeric micelle with high drug loading, a telodendrimer micelle was developed as a nanocarrier for fulvestrant, as an example of a drug that has extremely poor water solubility (sub nanomolar range). Telodendrimers were prepared by synthesis of a hydrophilic linear poly(sarcosine) and growing a lysine dendron from the chain terminal amine by a divergent synthesis. At the periphery of the dendritic block, 4, 8, and 16 fulvestrant molecules were conjugated to the lysine dendron creating a hydrophobic block. Having drug as part of the carrier not only reduces the usage of the inert carrier materials but also prevent the drugs from leakage and premature release by diffusion. The self-assembled telodendrimer micelles demonstrated good colloidal stability (CMC < 2 µM) in buffer and were uniform in size. In addition, these telodendrimer micelles could solubilize additional fulvestrant yielding an excellent overall drug loading capacity of up to 77 wt.% total drug load (summation of conjugated and encapsulated). Importantly, the size of the micelles could be tuned between 25-150 nm by controlling (i) the ratio between hydrophilic and hydrophobic blocks and (ii) the amount of encapsulated fulvestrant. The versatility of these telodendrimer-based micelle systems to both conjugate and encapsulate drug with high efficiency and stability, in addition to possessing other tuneable properties makes it a promising drug delivery system for a range of active pharmaceutical ingredients and therapeutic targets.

Preparation of Cationic Amphiphilic Nanoparticles with Modified Chitosan Derivatives for Doxorubicin Delivery

Polymeric micelle-like nanoparticles have demonstrated effectiveness for the delivery of some poorly soluble or hydrophobic anticancer drugs. In this study, a hydrophobic moiety, deoxycholic acid (DCA) was first bonded on a polysaccharide, chitosan (CS), for the preparation of amphiphilic chitosan (CS-DCA), which was further modified with a cationic glycidyltrimethylammounium chloride (GTMAC) to form a novel soluble chitosan derivative (HT-CS-DCA). The cationic amphiphilic HT-CS-DCA was easily self-assembled to micelle-like nanoparticles about 200 nm with narrow size distribution (PDI 0.08–0.18). The zeta potential of nanoparticles was in the range of 14 to 24 mV, indicating higher positive charges. Then, doxorubicin (DOX), an anticancer drug with poor solubility, was entrapped into HT-CS-DCA nanoparticles. The DOX release test was performed in PBS (pH 7.4) at 37 °C, and the results showed that there was no significant burst release in the first two hours, and the cumulative release increased steadily and slowly in the following hours. HT-CS-DCA nanoparticles loaded with DOX could easily enter into MCF-7 cells, as observed by a confocal microscope. As a result, DOX-loaded HT-CS-DCA nanoparticles demonstrated a significant inhibition activity on MCF-7 growth without obvious cellular toxicity in comparison with blank nanoparticles. Therefore, the anticancer efficacy of these cationic HT-CS-DCA nanoparticles showed great promise for the delivery of DOX in cancer therapy.