Boronate-mediated biologic delivery

Inefficient cellular delivery limits the landscape of macromolecular drugs. Boronic acids readily form boronate esters with the 1,2- and 1,3-diols of saccharides, such as those that coat the surface of mammalian cells. Here pendant boronic acids are shown to enhance the cytosolic delivery of a protein toxin. Thus, boronates are a noncationic carrier that can deliver a polar macromolecule into mammalian cells.     

Polymers for DNA delivery

Nucleic acid delivery has many applications in basic science, biotechnology, agriculture, and medicine. One of the main applications is DNA or RNA delivery for gene therapy purposes. Gene therapy, an approach for treatment or prevention of diseases associated with defective gene expression, involves the insertion of a therapeutic gene into cells, followed by expression and production of the required proteins. This approach enables replacement of damaged genes or expression inhibition of undesired genes. Following two decades of research, there are two major methods for delivery of genes. The first method, considered the dominant approach, utilizes viral vectors and is generally an efficient tool of transfection. Attempts, however, to resolve drawbacks related with viral vectors (e.g., high risk of mutagenicity, immunogenicity, low production yield, limited gene size, etc.), led to the development of an alternative method, which makes use of non-viral vectors. This review describes non-viral gene delivery vectors, termed "self-assembled" systems, and are based on cationic molecules, which form spontaneous complexes with negatively charged nucleic acids. It introduces the most important cationic polymers used for gene delivery. A transition from in vitro to in vivo gene delivery is also presented, with an emphasis on the obstacles to achieve successful transfection in vivo.     

Microemulsions as delivery systems

Solubilization capacity, dissolution efficiency, rate and extent of solute delivery are dependent on the microemulsion microstructure.     

Cyclodextrin-based gene delivery systems

Cyclodextrin (CD) history has been largely dominated by their unique ability to form inclusion complexes with guests fitting in their hydrophobic cavity. Chemical funcionalization was soon recognized as a powerful mean for improving CD applications in a wide range of fields, including drug delivery, sensing or enzyme mimicking. However, 100 years after their discovery, CDs are still perceived as novel nanoobjects of undeveloped potential. This critical review provides an overview of different strategies to promote interactions between CD conjugates and genetic material by fully exploiting the inside-outside/upper-lower face anisotropy of the CD nanometric platform. Covalent modification, self-assembling and supramolecular ligation can be put forward with the ultimate goal to build artificial viruses for programmed and efficient gene therapy (222 references).     

Charge-reversal amphiphiles for gene delivery

Delivering a missing gene or a functional substitute of a defective gene has the potential to revolutionize current medical care. Of the two gene delivery approaches, viral and synthetic vectors, synthetic cationic vectors possess several practical advantages but suffer from poor transfection efficiency. A new approach to gene delivery using charge-reversal amphiphiles is described. This synthetic vector transforms from a cationic to an anionic amphiphile intracellularly. This amphiphile performs two roles: first, it binds and then releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes lipid bilayers. A charge-reversal amphiphile was synthesized and fully characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using these vectors compared to current cationic amphiphiles.     

Polymeric conjugates for drug delivery

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both "see and treat" patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status.     

Cyclodextrins as cosmetic delivery systems

Aim of this work was the study of ferulic acid/cyclodextrin (CD) association complexes. Ferulic acid (FA) is a compound well-known as antioxidant and photoprotective agent (approved in Japan as sunscreen). Notwithstanding this, it is poorly suited for cosmetic applications because it undergoes functional and organoleptic modifications, when it is exposed to air, UV-light and heat. For this reason we prepared a set of FA/CD complexes with the aim to improve its physico-chemical stability. The inclusion complexes were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and nuclear magnetic resonance (¹H-NMR). The FA/α-CD complex showed the most promising properties (high association constant, high degree of photostability, slower FA release) as sunscreen delivery system.     

Liposome-based delivery of biological drugs

Biological drugs are attracting tremendous attention in disease treatment. However, their application is significantly limited by their inherent properties, such as high hydrophilicity, poor membranepermeability, low stability, and larger size. Liposome-based drug delivery systems are emerging as promising tools to improve their delivery, owing to their ability to reduce toxicity, improve bioavailability,and enhance the therapeutic efficacy of the drug by optimizing delivery to the specific targ...     

Biodegradable polyphosphazenes for drug delivery

Polyphosphazene derivatives having amino acid ester side groups were prepared by reaction of poly(dichlorophosphazene) with ethyl esters of amino acids. The in vitro degradation studies demonstrated that the rate of degradation depends on the nature of the amino acids. Introducing small amounts of hydrolytically sensitive groups such as depsipeptide ester or hydrolysis-catalysing moieties, such as histidine ethyl ester co-substituents, resulted in an increase of the degradation. The rate of hydrolytic degradation of the polyphosphazene material could be controlled by the content of the hydrolytically sensitive side groups or by blending hydrolysis-sensitive polymers with more stable derivatives. The results obtained from the in vivo implantation of biodegradable polyphosphazenes in mice indicate that the materials are very well tolerated by the animal body. Biodegradable polyphosphazenes have been used as matrix for the design of drug delivery systems. The rate of the in vitro release of mitomycin C from biodegradable polyphosphazenes can be controlled by changing the chemical composition of the polymer or by blending polymers of different chemical compositions.     

Collagen-based biomaterials for ibuprofen delivery

Drug delivery systems based on collagen sponges have increasingly become interesting materials for different medical applications. In this paper we present the obtaining, characterization and in vitro release of ibuprofen from collagen-based biomaterials in the form of sponges. The structural and morphological characteristics of these materials were investigated by infrared spectroscopy (FT-IR) and water uptake tests. Collagenase degradation, anti-inflammatory drug release and the kinetic mechanism are also discussed. The results obtained suggest that these new systems based on collagen have good potential for sustained release of analgesic and anti-inflammatory agents such as ibuprofen and the combination of collagen and ibuprofen as a sponge is a promising therapeutic method for the treatment of dental problems.     

Cellulose esters in drug delivery

Cellulose esters have played a vital role in the development of modern drug delivery technology. They possess properties that are not only well-suited to the needs of pharmaceutical applications, but that enable construction of drug delivery systems that address critical patient needs. These properties include very low toxicity, endogenous and/or dietary decomposition products, stability, high water permeability, high T _g, film strength, compatibility with a wide range of actives, and ability to form micro- and nanoparticles. This suite of properties has enabled the creation of a wide range of drug delivery systems employing cellulose esters as key ingredients. The following is a review of the most important types of these systems, and of the critical roles played by cellulose esters in making them work, focusing on more recent developments.     

Silica nanocapsules for redox-responsive delivery

Redox-responsive silica nanocapsules with a hydrophobic liquid core were synthesized by reactive templating of miniemulsion droplets with functional alkoxysilanes. Tetrasulfide bridges were successfully introduced into the inorganic shell and were found to be accessible for chemical reactions as shown by ³¹P-NMR spectroscopy. Indeed, the tetrasulfide groups could be reduced to yield thiol groups. A subsequent increase of permeability of the silica shell was observed upon reduction of the tetrasulfide groups.     

Mesoporous materials for drug delivery

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.     

Ultrasonically controlled polymeric drug delivery

The area of polymeric controlled drug delivery systems has been a field of increasing interest. However, relatively little attention has been given to developing systems in which the rate of delivery can be manipulated externally. We now report that release rates of biologically active substances from a polymeric matrix can be repeatedly modulated from a position external to the environment of use by ultrasonic energy. The ultrasound affects the degradation rate of bioerodible polymers as well as permeation through non-erodible polymers. The system has been shown to be responsive in vivo. Skin histopathology of the ultrasound treated area didn't reveal any differences between the treated skin and the untreated controls.     

Polyaspartamide-graft-polymethacrylate nanoparticles for doxorubicin delivery

A new PHEA‐IB‐PMANa⁺ copolymer has been synthesized and its pH‐induced self‐assembly has been investigated in an aqueous medium. PHEA‐IB‐PMANa⁺ formed nanoparticles with diameters from 25 to 50 nm upon protonation of the carboxylic acid moieties dislocated along the grafted polymethacrylate sodium salt side chains. The physico‐chemical characterization of the nanoparticles was performed using light scattering, zeta‐potential measurements, SEM, and AFM. Doxorubicin‐loaded nanoparticles were prepared and drug release profiles were evaluated under conditions mimicking physiological media. A biological characterization was carried out by testing the cytotoxicity on Caco‐2 cells, and cellular uptake on mouse monocyte macrophage (J774 A.1) and Caco‐2 cells.

     

Calibrant delivery for mass spectrometry

This article describes a means of sampling ions that are created at a location remote from the primary ion source used for mass spectral analysis. Such a source can be used for delivery of calibrant ions on demand. Calibrant ions are sprayed into an atmospheric pressure chamber, at a position substantially removed from the sampling inlet. A gas flow sweeps the calibrants towards the sampling inlet, and a new means for toggling the second ion beam into the instrument can be achieved with the use of a repelling field established by an electrode in front of the sampling inlet. The physical separation of two or more sources of ions eliminates detrimental interactions due to gas flows or fields. When using a nanoflow electrospray tip as the primary ion source, the potential applied to the tip completely repels calibrant ions and there is no compromise in terms of electrospray performance. When calibrant ions are desired, the potential applied to the nanoflow electrospray tip is lowered for a short period of time to allow calibrant ions to be sampled into the instrument, thus providing a means for external calibration that avoids the typical complications and compromises associated with dual spray sources. It is also possible to simultaneously sample ions from multiple ion beams if necessary for internal mass calibration purposes. This method of transporting additional ion beams to a sampling inlet can also be used with different types of atmospheric pressure sources such as AP MALDI, as well as sources configured to deliver ions of different polarity.