A pH‐sensitive polymer was synthesized by introducing the N‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting.
A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time‐controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded‐micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water‐insoluble (indomethacin) and water‐soluble drugs (gentamicin).
The pH sensitivity of a series of PbAEs synthesized from primary amines and diacrylates is studied. By changing alkyl groups of the amine monomers, the pKb can be tuned across a broad range (from 3.5 to 7.2). Micelles formed from a PEG‐PbAE block copolymer retain the pH sensitivity of PbAE and can stably load hydrophobic molecules under neutral pH, while quickly dissociate and release their cargoes at pH ≈ 6.0. When the chemotherapy drug DOX is loaded, the micelles show efficient cell proliferation inhibition to HeLa cells and fast intracellular release. Thus, the primary‐amine‐based PbAEs are shown to be promising in the construction of intracellular targeting drug delivery systems.
A new type of fluorescent polymeric micelles is developed by self‐assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)‐b‐poly[styrene‐co‐(2‐(1,2,3,4,5‐pentaphenyl‐1H‐silol‐1‐yloxy)ethyl methacrylate)] [PEG‐b‐P(S‐co‐PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX‐loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX‐loaded micelles.
CDDP is loaded into methoxypoly(ethylene glycol)‐block‐poly(L ‐glutamic acid) (mPEG‐b‐PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP‐loaded micelles show sustained cisplatin release in PBS, dose‐ and time‐dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP‐loaded micelles show an evident anti‐tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP‐loaded micelles and co‐administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG‐b‐PLG‐loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC.
Thermosensitive PNVCL‐b‐PEG block copolymer coupled with folic acid was prepared as an anti‐cancer drug carrier. This polymer self‐assembled into stable micelles in aqueous solutions at above 33 °C. At 37 °C, the release profile of PNVCL‐b‐PEG‐FA micelles showed a slower and more controlled release of the entrapped 5‐FU than that at 25 °C. The blank and 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles did not induce remarkable cytotoxicity against the EA.hy 926 human endothelial cell line; however, 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles showed a cytotoxicity effect against 4T1 mouse mammary carcinoma cells due to the availability of loaded anti‐cancer drugs delivered to the inside of the cancer cells by the folate‐receptor‐mediated endocytosis process.
A highly effective drug carrier is constructed by coating folic acid‐terminated poly(ethylene glycol) (PEG‐FA) on single walled carbon nanotubes (SWNTs) in a facile non‐covalent method. The anti‐cancer drug, doxorubicin (DOX), is further loaded on the surface of SWNTs at a very high loading efficiency, 149.3 ± 4.1%. The drug system (DOX/PEG‐FA/SWNTs) exhibits excellent stability under neutral pH conditions such as serum, but dramatically releases DOX at reduced pH typical of the tumour environment and intracellular lysosomes and endosomes. With the help of FA, DOX/PEG‐FA/SWNTs tend to selectively attach onto cancer cells and enter the lysosomes or endosomes by clathrin‐mediated endocytosis. This can greatly improve the pharmaceutical efficiency and reduce potential side effects.
Thiolated Pluronic (Plu‐SH) nanoparticles are developed as potential articulate, target‐specific anticancer‐drug carriers for intracellular drug release triggered by the difference in redox potential in tumor cells. The cores of the micelles are formed by the disulfide bonds of the functionalized Pluronic F127, when dissolved in an aqueous solution. The nanoparticles are 95.6 ± 18.6 nm in size, and 235.6 ± 63.7 nm after encapsulation of the hydrophobic drug molecules. The drug‐loaded micelles show effective stability in blood‐plasma conditions and the kinetics of micelle stability and drug release are shown. Paclitaxel‐loaded micelles display approximately 39% cell viability in A549 cells.
Novel ‘nano in nano’ composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound‐loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide‐co‐glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye‐loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release.
Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS‐b‐PAA and PS‐b‐P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.‐%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution.