Drug Encapsulation In Micelles Research Articles

Nanostructrue and Function of PEGylated Phospholipid Micelles Encapsulation Drugs

We developed one-step self-assembly method to prepare poly(ethylene glycol)-phosphatidylethanolamine(PEG-PE) micelles, which had core-shell structure and particle size at 20 nm. Drug-loaded PEG-PE micelles displayed better stability than empty micelles in vitro and in vivo because the drug/polymer interactions reinforced the micellular structure. Drugs distributed at the core-shell interface of PEG-PE micelles without changing micellar size. Our studies demonstrated that physico-chemical properties of drugs determined their self-assembly mechanism with polymers and the release profiles of drugs from micelles in vitro. Encapsulation of drugs in micelles increased their cellular accumulation due to the increased membrane fluidity caused by PEG-PE insertion, which did not affect cell membrane permeability and integrity. Compared to free drugs, anticancer drugs encapsulated into PEG-PE micelles demonstrated an increased antitumor efficiency in vivo and an extended life span of mice by EPR effect of PEG-PE micelles. On the other hand, PEG-PE micelles maintained higher drug concentrations in lymphatic systems, thus resulting in significantly antitumor effects for metastatic tumors with less lung metastasis. PEG-PE is an FDA-approved nonionic diblock copolymer with good biocompatibility and safety. As drug delivery systems, PEG-PE micelles has a wide developmental future.

Ultrasound-mediated micellar drug delivery

During the last decade, nanomedicine has emerged as a new field of medicine that utilises nanoscale materials for delivery of drugs, genes and imaging agents. The efficiency of drug delivery may be enhanced by the application of directed energy, which provides for drug targeting and enhanced intracellular uptake. In this paper, we present a review of recent advances in the ultrasound-mediated drug delivery with the emphasis on polymeric micelles as tumour-targeted drug carriers. This new modality of drug targeting to tumours is based on the drug encapsulation in polymeric micelles followed by a localised release at the tumour site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of free drug and provides for a passive drug targeting to tumours via the enhanced permeability and retention (EPR) effect, therefore reducing unwanted drug interactions with healthy tissues. Ultrasound affects micellar drug delivery on various levels. Mild hyperthermia induced by ultrasound may enhance micelle extravasation into tumour tissue; mechanical action of ultrasound results in drug release from micelles and enhances the intracellular uptake of both released and encapsulated drug. In addition, polymeric micelles sensitise multidrug resistant (MDR) cells to the action of drugs.

Delivery of drugs to cell membranes by encapsulation in PEG–PE micelles

Developing polymer micelles as drug delivery systems requires an in-depth understanding of how they interact with cells and deliver drugs across the cell membrane; however, this investigation faces many problems. In this study, we attempt to show how polyethylene glycol–phosphatidylethanolamine (PEG–PE) micelles deliver drugs across cell membranes by using a series of fluorescence techniques, including de-quenching, FRET and multi-labeling. We demonstrate that PEG–PE copolymers transfer to the cell membrane from micelles due to their amphiphilic properties, and are then internalized through nonspecific endocytosis and distributed in the endoplasmic reticulum and Golgi apparatus without affecting cellular ATP and viability. Hydrophilic drugs and/or hydrophobic dyes can be encapsulated in PEG–PE micelles, which are maintained in an intact form in culture medium before and after incubation with cells. These micelles disassemble and release their payloads at the cell membrane; released agents are accelerated to enter cells due to the increased membrane fluidity caused by PEG–PE insertion. Encapsulation of drugs in micelles does not change their intracellular distribution but increases their cellular accumulation. This investigation provides new insights into the mechanism of polymer micelle delivering drugs into cells, which are helpful for designing a true site-specific delivery carrier.

Combined cancer therapy by micellar-encapsulated drug and ultrasound

A new modality of drug targeting to tumors that is under development in our lab is based on the drug encapsulation in polymeric micelles followed by a localized release at the tumor site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of drug and provides for a passive drug targeting to tumors via the enhanced penetration and retention (EPR) effect, thus, reducing unwanted drug interactions with healthy tissues. In addition, polymeric micelles sensitize multidrug resistant (MDR) cells to the action of drugs. Upon the accumulation of drug-loaded micelles at the tumor site, ultrasonic irradiation of the tumor is used to provide for the effective intracellular drug uptake. Ultrasound releases drug from micelles and enhances the intracellular uptake of both released and encapsulated drug. An important advantage of ultrasound is that it is noninvasive, can penetrate deep into the interior of the body, can be focused and carefully controlled. The results of the in vitro application of this technique for delivering anthracyclin drugs to ovarian carcinoma A2780 drug-sensitive and MDR cells are described.

Combined cancer therapy by micellar-encapsulated drug and ultrasound

A new modality of drug targeting to tumors that is under development in our lab is based on the drug encapsulation in polymeric micelles followed by a localized release at the tumor site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of drug and provides for a passive drug targeting to tumors via the enhanced penetration and retention (EPR) effect, thus, reducing unwanted drug interactions with healthy tissues. In addition, polymeric micelles sensitize multidrug resistant (MDR) cells to the action of drugs. Upon the accumulation of drug-loaded micelles at the tumor site, ultrasonic irradiation of the tumor is used to provide for the effective intracellular drug uptake. Ultrasound releases drug from micelles and enhances the intracellular uptake of both released and encapsulated drug. An important advantage of ultrasound is that it is noninvasive, can penetrate deep into the interior of the body, can be focused and carefully controlled. The results of the in vitro application of this technique for delivering anthracyclin drugs to ovarian carcinoma A2780 drug-sensitive and MDR cells are described.

Ultrasound-triggered drug targeting of tumors in vitro and in vivo

The new modality of drug targeting of tumors that we are currently developing is based on drug encapsulation in polymeric micelles, followed by the localized release at the tumor site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of drug, diminishes intracellular drug uptake by normal cells, and provides passive drug targeting of tumors, thus reducing unwanted drug interactions with healthy tissues. Ultrasound irradiation is used to release drug from micelles at the tumor site and to enhance the intracellular drug uptake by tumor cells. An important advantage of ultrasound is that it is noninvasive, can penetrate deep into the interior of the body, can be focused and carefully controlled. Here we describe factors involved in the ultrasound interaction with viable cells in the absence and presence of drug carriers and anti-cancer drugs. We present in vivo effects of 1 MHz ultrasound on drug biodistribution, intratumoral distribution, and survival rates of immuno-compromised athymic nu/nu mice bearing ovarian carcinoma tumors.