Intelligent Micelles Research Articles

Intelligent micelles for on-demand drug delivery targeting extracellular matrix of pancreatic cancer

As a key pathological feature of pancreatic ductal adenocarcinoma(PDAC), the dense extracellular matrix(ECM) limits the penetration of chemotherapy drugs and is involved in the formation of immunosuppressive microenvironment. Meanwhile, clinical practice has shown that the treatment strategy for ECM should consider its restriction of tumor cell metastasis, and the need for in-depth chemotherapy without destroying ECM is proposed. STAT3 inhibitors have been reported to regulate tumor microenvironment including interrupt the form of ECM. Therefore, we designed and established a micelle system MP@HA with in vivo targeting and responsive drug release function co-loading gemcitabine monophosphate and STAT3 inhibitor silibinin. The hyaluronic acid on the surface of the micelle can bind specifically to the CD44 molecule on the surface of tumor cells and help micelles accumulate at the tumor site. The nitroimidazole used to modify the polymeric skeleton can make the micellar structure collapse in response to hypoxia reduction conditions in the tumor environment, and release silibinin to widely regulate STAT3 molecules in the PDAC microenvironment. The polymer fragment attached with gemcitabine monophosphate can penetrate deep into PDAC tumors due to its small size and positive charge exposed, achieving deep chemotherapy. This research indicates a promising micelle system meeting complicated demands proposed in PDAC treatment to improve antitumor efficacy.

Multiple stimulus-response berberine plus baicalin micelles with particle size-charge-release triple variable properties for breast cancer therapy

Objective The aim was to develop a nanoscale drug delivery system with enzyme responsive and acid sensitive particle size and intelligent degradation aiming to research the inhibitory effect on breast cancer. Significance The delivery system addressed the problems of tissue targeting, cellular internalization, and slow drug release at the target site, which could improve the efficiency of drug delivery and provide a feasible therapeutic approach for breast cancer. Methods The acid sensitive functional material DSPE-PEG2000-dyn-PEG-R9 was synthesized by Michael addition reaction. Then, the berberine plus baicalin intelligent micelles were prepared by thin-film hydration. Subsequently, we characterized the physical and chemical properties of berberine plus baicalin intelligent micelles, evaluated its anti-tumor effects in vivo and in vitro. Results The target molecule was successfully synthesized, and the intelligent micelles showed excellent chemical and physical properties, delayed drug release and high encapsulation efficiency. In vitro and in vivo experiments also confirmed that the intelligent micelles could effectively target tumor sites, penetrate tumor tissues, enrich in tumor cells, inhibit tumor cell proliferation, inhibit tumor cell invasion and migration, and induce tumor cell apoptosis. Conclusion Berberine plus baicalin intelligent micelles have excellent anti-tumor effects and no toxicity to normal tissues, which provides a new potential drug delivery strategy for the treatment of breast cancer.

Amphiphilic copolymers with light-pH-temperature triple stimuli-responses: Preparation, self-assembly and controlled drug release

Poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate)-block-poly(methacrylic acid-co-spiropyran methacrylate) (P(MEO2MA-co-OEGMA)-b-P(MAA-co-SPMA)) was prepared by atom transfer radical polymerization (ATRP), acidolysis and dicyclohexylcarbodiimide (DCC) reaction and can self-assemble into spherical micelles. Poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate) (P(MEO2MA-co-OEGMA)) segment can respond to changes in temperature, and poly(methacrylic acid) (PMAA) segments show pH-responsive property. The reversible conversion between spiropyran (SP) which is hydrophobic and hydrophilic anthocyanins H+(MCH)/anthocyanins (MC) makes the poly(spiropyran methacrylate) (PSPMA) segments show light-pH-temperature triple-stimulus responses. As a result, the micelles presented light, pH and temperature triple stimuli-responsive properties. The micelles showed different sizes and morphologies under different environmental stimuli. Therefore, the intelligent micelles could be used as the carrier for the multiple controlled release of doxorubicin (DOX) drug molecules.

Intelligent Drug Delivery Systems: Polymeric Micelles and Hydrogels

Advanced drug delivery systems try to adjust the site and/or the rate of the release to the physiological conditions of the patient, to the progression of the illness, or to the circadian rhythms. Being different from classical pre-programmed controlled release dosage forms, the new devices aim to provide the drug release profile best for the needs of each patient. Intelligent drug delivery systems are mostly based on stimuli-responsive polymers which sense a change in a specific variable and activate the delivery; this phenomenon being reversible. This review reports on recent advances in the development of open-loop and closed-loop control systems based on stimuli-responsive polymers and their application in the drug delivery field as pulsatile and self-regulated devices. The aim of this review is to describe the most recent advances in the development of intelligent micelles and hydrogels which are sensitive to pH, specific molecules (with a mention to the molecular imprinting), temperature, irradiation or electric field, and the applications of which these mechanisms are intended.