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Advanced Drug Delivery Reviews (v.63, #9)
Layer-by-layer self-assembled nanoshells for drug delivery
by Melgardt M. de Villiers Theme Editor; Yuri M. Lvov Theme Editor (pp. 699-700).
Introduction to nanocoatings produced by layer-by-layer (LbL) self-assembly by Melgardt M. de Villiers; Daniel P. Otto; Schalk J. Strydom; Yuri M. Lvov (pp. 701-715).
Studies on the adsorption of oppositely charged colloidal particles ultimately resulted in multilayered polyelectrolyte self-assembly. The inception of layer-by-layer constructed particles facilitated the production of multifunctional, stimuli-responsive carrier systems. An array of synthetic and natural polyelectrolytes, metal oxides and clay nanoparticles is available for the construction of multilayered nanocoats on a multitude of substrates or removable cores. Numerous substrates can be encapsulated utilizing this technique including dyes, enzymes, drugs and cells. Furthermore, the outer surface of the particles presents and ideal platform that can be functionalized with targeting molecules or catalysts. Some processing parameters determining the properties of these successive self-assembly constructs are the surface charge density, coating material concentration, rinsing and drying steps, temperature and ionic strength of the medium. Additionally, the simplicity of the layer-by-layer assembly technique and the availability of established characterization methods, render these constructs extremely versatile in applications of sensing, encapsulation and target- and trigger-responsive drug delivery.Display Omitted
Keywords: Layer-by-layer; Nanocoating; Self-assembly; Polyelectrolyte; Adsorption
Remote control over guidance and release properties of composite polyelectrolyte based capsules by Maria N. Antipina; Gleb B. Sukhorukov (pp. 716-729).
Polyelectrolyte multilayer capsules represent a unique tool to fabricate micron- and submicron-sized delivery systems with the properties of external guidance by means of remote physical influence. Embedding of nanoparticles into polyelectrolyte multilayer constructs opens up the opportunities to navigate the capsules with magnetic field and in-situ trigger the release of encapsulated material in response to the physical stimuli, such as light and ultrasound. So far, optically- and magnetically-induced addressing of the polyelectrolyte multilayer capsules internalized by the living cells in-vitro has been demonstrated. In this review, we discuss the state of the art, future perspectives and anticipated obstacles of in-vivo and in-vitro applications of the polyelectrolyte capsules performing remotely controlled release delivery of bioactives.Display Omitted
Keywords: Abbreviations; BSA; bovine serum albumin; FITC; fluorescein isothiocyanate; HB; hypocrellin B; HFMF; high frequency magnetic field; IR; infrared; MF; melamine formaldehyde; MRI; magnetic resonance imaging; PDT; photodynamic therapy; PEG; polyethylene glycol; PDADMAC; poly(diallyldimethylammonium chloride); PAH; poly(allylamine hydrochloride); PSS; poly(styrene sulfonate); REI; polyethyleneimine; PMAMVE; poly(maleic anhydride-altmethyl vinyl ether); PS; polystyrene; RBC; red blood cells; RF; radio frequencyDrug delivery; Polyelectrolyte capsules; Remotely controlled release; Ultrasound; Magnetic capsules; Light addressable capsules
Stimuli-responsive LbL capsules and nanoshells for drug delivery by Mihaela Delcea; Mohwald Helmuth Möhwald; André G. Skirtach (pp. 730-747).
Review of basic principles and recent developments in the area of stimuli responsive polymeric capsules and nanoshells formed via layer-by-layer (LbL) is presented. The most essential attributes of the LbL approach are multifunctionality and responsiveness to a multitude of stimuli. The stimuli can be logically divided into three categories: physical (light, electric, magnetic, ultrasound, mechanical, and temperature), chemical (pH, ionic strength, solvent, and electrochemical) and biological (enzymes and receptors). Using these stimuli, numerous functionalities of nanoshells have been demonstrated: encapsulation, release including that inside living cells or in tissue, sensors, enzymatic reactions, enhancement of mechanical properties, and fusion. This review describes mechanisms and basic principles of stimuli effects, describes progress in the area, and gives an outlook on emerging trends such as theranostics and nanomedicine.Display Omitted
Keywords: Stimuli; Capsules; LbL; Enzymes; Theranostics; Nanomedicine; Encapsulation
Polymeric multilayer capsules delivering biotherapeutics by Stefaan De Koker; Liesbeth J. De Cock; Pilar Rivera-Gil; Wolfgang J. Parak; Auzely Velty Rachel Auzély Velty; Chris Vervaet; Jean Paul Remon; Johan Grooten; Bruno G. De Geest (pp. 748-761).
Polymeric multilayer capsules have emerged as a novel drug delivery platform. These capsules are fabricated through layer-by-layer sequential deposition of polymers onto a sacrificial core template followed by the decomposition of this core yielding hollow capsules. The resulting nanometer thin membrane is permselective, allowing diffusion of water and ions but excluding larger molecules. Moreover, the sequential fabrication procedure allows a precise fine-tuning of the capsules’ physicochemical and biological properties. These properties have put polymeric multilayer capsules under major attention in the field of drug delivery. In this review we focus on polymeric multilayer capsule mediated delivery of biotechnological macromolecular drugs such as peptides, proteins and nucleic acids.Display Omitted
Keywords: Encapsulation; Drug delivery; Layer-by-layer; Vaccine; Gene therapy; Antigen; Targeting
Layer-by-layer self-assembled shells for drug delivery by Katsuhiko Ariga; Yuri M. Lvov; Kohsaku Kawakami; Qingmin Ji; Jonathan P. Hill (pp. 762-771).
There are several requirements for the safe and effective delivery of therapeutic agents for human use. Direct injection of drugs may cause side effects due to their permeation to other, undiseased regions of the body so that concealment and targeting with appropriate materials is a critical consideration in the design of practical drug delivery systems. In particular, carriers with structures which can be flexibly controlled are more useful since functional structure units can be assembled in component-by-component and/or layer-by-layer fashion. In this review, we focus on preparation of layer-by-layer shells directed at drug delivery applications. After a description of the fundamentals of layer-by-layer (LbL) assembly, recent progress in the field of self-assembled microshells and nanoshells for drug delivery applications are summarized. In addition, concepts developed to solve current difficulties are also described. Encapsulation of insoluble drugs in nanoshells and their delivery can satisfy some of the demands of practical medical use. Thus, aqueous suspensions of insoluble drugs have been subjected to powerful ultrasonic treatment followed by sequential addition of polycations and polyanions to the particle solution leading to assembly of ultra-thin polyelectrolyte shells on the nano-sized drug particles. In another innovative example, stepwise release of drugs from LbL films of mesoporous capsules to the exterior in the absence of external stimuli was demonstrated. It can be regarded as stimuli-free auto-modulated material release.Display Omitted
Keywords: Layer-by-layer assembly; Shell; Drug delivery; Insoluble drugs; Auto-modulated material release
Layer-by-layer capsules for magnetic resonance imaging and drug delivery by Hua Ai (pp. 772-788).
Layer-by-layer (LbL) self-assembled polyelectrolyte capsules have demonstrated their unique advantages and capability in drug delivery applications. These ordered micro/nano-structures are also promising candidates as imaging contrast agents for diagnostic and theranostic applications. Magnetic resonance imaging (MRI), one of the most powerful clinical imaging modalities, is moving forward to the molecular imaging field and requires the availability of advanced imaging probes. In this review, we are focusing on the design of MRI visible LbL capsules, which incorporate either paramagnetic metal-ligand complexes or superparamagnetic iron oxide (SPIO) nanoparticles. The design criteria cover the topics of probe sensitivity, biosafety, long-circulation property, targeting ligand decoration, and drug loading strategies. Examples of MRI visible LbL capsules with paramagnetic or superparamagnetic moieties were given and discussed. This carrier platform can also be chosen for other imaging modalities.Display Omitted
Keywords: Abbreviations; BLI; bioluminescence imaging; CEST; chemical exchange saturation transfer; CH; chitosan; CT; computed tomography; d; aer; aerodynamic diameter; FLI; fluorescence imaging; HA; hyaluronic acid; LbL; layer-by-layer; MF; melamine formaldehyde; MR; magnetic resonance; MRI; magnetic resonance imaging; NSF; nephrogenic systemic fibrosis; q; hydration number; PAA; poly(acrylic acid); PAH; poly(allylamine) hydrochloride; PAS; poly(anetholesulfonic acid); PASP; poly-; l; -aspartic acid; PE; polyelectrolyte; PEI; polyethylenimine; PEG; poly(ethylene glycol); PET; positron emission tomography; PGA; poly-; l; -glutamic acid; PLL; poly-; l; -lysine; PSS; poly(styrenesulfonate); r; 1; longitudinal relaxivity; r; 2; transverse relaxivity; RES; reticuloendothelial system; SPECT; single photon emission computed tomography; SBM; Solomon–Bloembergen–Morgan; T; 1; longitudinal relaxation time; T; 2; transverse relaxation time; τ; R; rotational correlation time; τ; M; residence time of the coordinated water moleculeLayer-by-layer; Self-assembly; Polyelectrolyte capsule; Magnetic resonance imaging; Paramagnetic; Superparamagnetic; Gadolinium; Iron oxide; Drug delivery; Molecular imaging
Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery by Challa S.S.R. Kumar; Faruq Mohammad (pp. 789-808).
Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled drug delivery through bond breaking (DBB) and hyperthermia-based controlled drug delivery through enhanced permeability (DEP). The review also covers, for the first time, core–shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms -towards successful application in personalized medicine.Display Omitted
Keywords: Hyperthermia; Hyperthermia-based therapy; Hyperthermia-based controlled drug delivery; Core–shell magnetic nanoparticles; Theranostics
pH- and sugar-sensitive layer-by-layer films and microcapsules for drug delivery by Katsuhiko Sato; Kentaro Yoshida; Shigehiro Takahashi; Jun-ichi Anzai (pp. 809-821).
The present review provides an overview on the recent progress in the development of pH- and sugar-sensitive layer-by-layer (LbL) thin films and microcapsules in relation to their potential applications in drug delivery. pH-sensitive LbL films and microcapsules have been studied for the development of peptide and protein drug delivery systems to the gastrointestinal tract, anti-cancer drugs to tumor cells, anti-inflammatory drugs to inflamed tissues, and the intracellular delivery of DNA, where pH is shifted from neutral to acidic. pH-induced decomposition or permeability changes of LbL films and microcapsules form the basis for the pH-sensitive release of drugs. Sugar-sensitive LbL films and microcapsules have been studied mainly for the development of an artificial pancreas that can release insulin in response to the presence of glucose. Therefore, glucose oxidase, lectin, and phenylboronic acid have been used for the construction of glucose-sensitive LbL films and microcapsules. LbL film-coated islet cells are also candidates for an artificial pancreas. An artificial pancreas would make a significant contribution to improving the quality of life of diabetic patients by replacing repeated subcutaneous insulin injections.Display Omitted
Keywords: LbL film; LbL microcapsule; pH-sensitive release; Sugar-sensitive release; Insulin release; Drug delivery
Polymer assemblies for controlled delivery of bioactive molecules from surfaces by Svetlana Pavlukhina; Svetlana Sukhishvili (pp. 822-836).
Localized delivery of bioactive compounds from surfaces of biomedical devices affords significant therapeutic benefits, and often relies on the capability of surface coatings to provide spatial and temporal control over release rate. The layer-by-layer technique presents a unique means to construct surface coatings that can conform to a variety of biomaterial surfaces and serve as matrices enabling controlled delivery of bioactive molecules from surfaces. The versatility of layer-by-layer assembly enables construction of surface coatings of diverse chemistry and internal architecture with controlled release properties. This review focuses on recent developments in constructing such layered matrices using linear polymers, polymer nanoparticles and block copolymer micelles, including micelles with stimuli-responsive cores, as film building blocks and in controlling release rate of therapeutics from these matrices via degradation, application of pH, ionic strength, temperature, light, electric field and chemical or biological stimuli. Challenges and opportunities associated with fabrication of stratified multilayer films capable of multi-stage delivery of multiple drugs are also discussed.Display Omitted
Keywords: Layer-by-layer; Surface; Controlled delivery of biomolecules; Polymers; Polymer nanoparticles; Block copolymer micelles
LbL coated microcapsules for delivering lipid-based drugs by Elena M. Shchukina; Dmitry G. Shchukin (pp. 837-846).
Nowadays, more than 40% of new pharmacologically active compounds exhibit poor water solubility, which requires the development of the new methods for their administration and delivery. One of the most promising approaches for the development of such delivery systems is the use of layer-by-layer assembly technology for encapsulation of the lipid-based drugs. This technique permits the step-wise adsorption of various components as the layer growth is governed by their electrostatic attraction and allows the formation of multilayer shells with nanometer-scale precision. The proposed review surveys the application of layer-by-layer assembly for emulsions, nanoparticles, and capsule-based delivery systems for lipid-based drugs.Display Omitted
Keywords: Layer-by-layer assembly; Hydrophilization; Lipophilic drug; Capsule; Polyelectrolyte shell; Ultrasonication
Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells by Viviana Vergaro; Flavia Scarlino; Claudia Bellomo; Rosaria Rinaldi; Daniele Vergara; Michele Maffia; Francesca Baldassarre; Gianluigi Giannelli; Xingcai Zhang; Yuri M. Lvov; Stefano Leporatti (pp. 847-864).
In this review we will overview novel nanotechnological nanocarrier systems for cancer therapy focusing on recent development in polyelectrolyte capsules for targeted delivery of antineoplastic drugs against cancer cells. Biodegradable polyelectrolyte microcapsules (PMCs) are supramolecular assemblies of particular interest for therapeutic purposes, as they can be enzymatically degraded into viable cells, under physiological conditions. Incorporation of small bioactive molecules into nano-to-microscale delivery systems may increase drug's bioavailability and therapeutic efficacy at single cell level giving desirable targeted therapy. Layer-by-layer (LbL) self-assembled PMCs are efficient microcarriers that maximize drug's exposure enhancing antitumor activity of neoplastic drug in cancer cells. They can be envisaged as novel multifunctional carriers for resistant or relapsed patients or for reducing dose escalation in clinical settings.Display Omitted
Keywords: Cancer therapy; Nanotechnology; Drug delivery; Nanocarriers; Microcapsules; Layer-by-layer; Polyelectrolyte multilayers