Polymeric micelles for oral drug administration enabling locoregional and systemic treatments (original) (raw)
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Polymeric micelles for oral drug delivery
European Journal of Pharmaceutics and Biopharmaceutics, 2010
In the case of chronic therapies, the oral route is often the preferred route for drug administration given its acceptability and convenience. However, various factors which limit drug absorption through the gastro-intestinal (GI) mucosa contribute to restricting the bioavailability of the drug, that is, the actual amount which reaches the bloodstream. Among these factors, poor drug permeability through the GI mucosa and/or low aqueous solubility are of central importance. Polymeric micelles, which form upon self-assembly of amphiphilic macromolecules, can act as vehicles for the oral delivery of these drugs. This manuscript summarizes the literature in relation to the design of these micellar systems and their characterization with respect to drug loading and retention properties as well as the ability to withstand dissociation and drug discharge upon oral administration. Also, the role of certain polymers in improving drug absorption through the GI mucosa, either by increasing membrane permeability to the drug and/ or carrier or by inhibiting drug efflux transporters in the GI mucosa, is discussed. Finally, this review reports other drug delivery strategies such as using bioadhesive polymers which may lengthen residence time in the GI tract and promote drug permeation, or rendering the polymeric micelles pH-sensitive in order to ensure drug release from the carrier at its site of absorption.
Polymeric Micelles for the Delivery of Poorly Soluble Drugs
John Wiley & Sons, Ltd eBooks, 2013
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Intestinal uptake and biodistribution of novel polymeric micelles after oral administration
Journal of Controlled Release, 2006
To determine the fate of polymeric micelles after oral administration, we investigated the possible transport of polymeric micelles across Caco-2 monolayers and their biodistribution in rats after per os administration of [ 14 C]-labelled mmePEG 750 P(CL-co-TMC) micelles containing risperidone (BCS Class II drug). mmePEG 750 P(CL-co-TMC) was able to cross Caco-2 monolayer via a saturable transport mechanism. The oral bioavailability of the polymer was 40%. Polymeric micelles based on mmePEG 750 P(CL-co-TMC) showed very low clearance by the reticuloendothelial system (RES) and a renal excretion. A sustained release of risperidone was observed.
Polymeric micelles in mucosal drug delivery: Challenges towards clinical translation
Biotechnology advances, 2015
Polymeric micelles are nanostructures formed by the self-aggregation of copolymeric amphiphiles above the critical micellar concentration. Due to the flexibility to tailor different molecular features, they have been exploited to encapsulate motley poorly-water soluble therapeutic agents. Moreover, the possibility to combine different amphiphiles in one single aggregate and produce mixed micelles that capitalize on the features of the different components substantially expands the therapeutic potential of these nanocarriers. Despite their proven versatility, polymeric micelles remain elusive to the market and only a few products are currently undergoing advanced clinical trials or reached clinical application, all of them for the therapy of different types of cancer and administration by the intravenous route. At the same time, they emerge as a nanotechnology platform with great potential for non-parenteral mucosal administration. However, for this, the interaction of polymeric mice...
Polymeric micelle as a multifunctional therapeutics
Polymeric micelles are nano-scopic core/shell structures produced by amphiphilic block copolymers with hydrophobic core and hydrophilic shell. Both the inherent and modifiable properties of polymeric micelles construct them particularly well appropriate for drug delivery purposes. In the last two decades, polymeric micelles have been vigorously studied as an innovative type of drug carrier system, because it possesses high stability both in vitro and in vivo and good biocompatibility, and can solubilize a broad variety of poorly soluble drugs. Polymeric micelles can overcome various limitations of the conventional drug delivery system, acting as carriers able to enhance drug absorption, protection of the loaded drug from the harsh environment of the GI tract, release of the drug in a controlled manner at target sites, prolongation of the residence time in the targeted area, and improve the drug accumulation in effectors area. In this review, polymeric micelle drug carrier systems are discussed with a spotlight on designs, types and classifications of the polymeric micelle system. Advantages and disadvantages are briefly summarized and explained, followed by delivery of different drug category.
Journal of Visualized Experiments, 2015
Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 µg/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 o C over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven.
Colloidal Drug Delivery Systems – Recent Advances With Polymeric Micelles
CHIMIA, 2008
With the emergence of nanotechnology in drug delivery, colloidal systems and particularly polymeric micelles have attracted great attention. Polymeric micelles formed by the self-assembly of amphiphilic copolymers adopt a core-shell structure, which can be loaded with drugs and used as drug delivery systems for various medical applications. The most interesting aspects involve extended blood circulation times and stability upon dilution, which enable polymeric micelles to accumulate in tumor or inflammation sites due to the enhanced permeation and retention effect (EPR). In the first part of this paper polymeric micelles with different morphologies and different circulating-, active- and passive targeting, and stimuli responsive properties will be reviewed. Furthermore amphiphilic block copolymers of different compositions for pharmaceutical micelle formulations will be discussed. The hydrophilic block is often composed of the biocompatible polyethylene glycol (PEG), whereas diverse...
Polymeric micelles as drug delivery vehicles
Though much progress has been made in drug delivery systems, the design of a suitable carrier for the delivery of hydrophobic drugs is still a major challenge for researchers. The use of micellar solutions of low molecular weight surfactants has been one of the popular methods for the solubilization of hydrophobic drugs; however, such surfactants suffer from high critical micelle concentration and concomitant low stabilities. In contrast to surfactants of low molecular masses, polymeric micelles are associated with general advantages like higher stability, tailorability, greater cargo capacity, non-toxicity and controlled drug release. Therefore, the current review article is focused on the engineering of the core of polymeric micelles for maximum therapeutic effect. For enhanced drug encapsulation capacity and getting useful insights into the controlled release mechanism we have reviewed the effects of temperature and pH on responsive polymeric micelles. The article also presents important research outcomes about mixed polymeric micelles as better drug carriers in comparison to single polymeric micelles.
Polymeric micelle as a nanocarrier for delivery of therapeutic agents: A comprehensive review
Journal of Drug Delivery and Therapeutics
For selective and effective drug delivery of therapeutic agent nanocarriers are the most effective agents. Micelles are an aggregate of surfactant molecules that dispersed in a liquid colloid. Micelles have a variety of shapes such as spheres, rods, vesicles, tubules, and lamellae. The shape and size of a micelle are a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. Poly Ethylene Glycol (PEG) is the most commonly used hydrophilic segment of micelles for drug delivery. Besides PEG, other polymers including poly (N-vinyl pyrrolidone) (PVP) and poly (N-isopropyl acrylamide) (pNIPAM) have also been used as hydrophilic portion of micelles. In this review we all discus about the polymeric micelles (PMs) as a nanocarriers for delivery of therapeutic agents. Keywords: Polymeric Micelles, Colloids, Nanocarriers, Drug Delivery, Poly Ethylene Glycol(PEG)
Micellar Carriers for the Delivery of Multiple Therapeutic Agents
Colloids and Surfaces B: Biointerfaces, 2015
Multi-drug therapy is described as a simultaneous or sequential administration of two or more drugs with similar or different mechanisms of action and is recognized as a more efficient solution to combat successfully, various ailments. Polymeric micelles (PMs) are self-assemblies of block copolymers providing numerous opportunities for drug delivery. To date various micellar formulations were studied for delivery of drugs, nutraceuticals and genes; a few of them are in clinical trials. It was observed that there is an immense need for the development of PMs embedding multiple therapeutic agents to combat various ailments, including cancers, HIV/AIDS, malaria, multiple sclerosis, hypertension, infectious diseases, cardiovascular and metabolic diseases, immune disorders and many psychiatric disorders. Several combinations of drug-drug, drug-nutraceutical, drug-gene and drug-siRNA explored to date are detailed in this review, with a special emphasis on their potential and future perspectives. A summary of various preparation methods, characterization techniques and applications of PMs are also provided. This review presents a holistic approach on multi-drug delivery using micellar carriers and emphasizes on the development of therapeutic hybrids embedding novel combinations for safer and effective therapy.