Controlled Drug Release Asymptotics

The solution of Higushi's model for controlled release of drugs is examined when the solubility of the drug in the polymer matrix is a prescribed function of time. A time-dependent solubility results either from an external control or from a change in pH due to the activation of pH immobilized enzymes. The model is described as a one-phase moving boundary problem which cannot be solved exactly. We consider two limits of our problem. The first limit considers a solubility much smaller than the initial loading of the drug. This limit leads to a pseudo-steady-state approximation of the diffusion equation and has been widely used when the solubility is constant. The second limit considers a solubility close to the initial loading of the drug. It requires a boundary layer analysis and has never been explored before. We obtain simple analytical expressions for the release rate which exhibits the effect of the time-dependent solubility

Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds

A novel Malonamide Periodic Mesoporous Organosilica (PMO) for controlled Ibuprofen release

Controlled drug release gained a sharply increasing interest over recent years. Multiple materials have been screened as possible drug carriers, ranging from biodegradable polymers to hydroxyapatite[1]. Periodic Mesoporous Organosilicas are valuable alternatives as they possess a high chemical and thermal stability combined with a biocompatible nature[2]. Furthermore, their large internal surface area permits a high drug loading. Careful selection of the organic ‘bridged’ functionality allows a controlled release with respect to external stimuli, such as pH or temperature, of the drugs which are adsorbed via weak and reversible interactions, e.g. H-bonding, ionic and hydrophobic-phobic interaction[3]. In this contribution a novel malonamide (MA-PMO) and a methyl-malonamide PMO (mMA-PMO) bearing a high amount of functionalities, capable of multiple intramolecular interactions, are developed and thoroughly characterized[4]. Subsequently, these hybrid materials are evaluated in the controlled drug release of Ibuprofen

Functional Polymers for Controlled Drug Release

This Special Issue focuses on the synthesis and characterization of hydrogels specifically used as carriers of biological molecules for pharmaceutical and biomedical employments. Pharmaceutical applications of hydrophilic materials has emerged as one of the most significant trends in the area of nanotechnology. To propose some of the latest findings in this field, each contribution involves an in-depth analysis including different starting materials and their physico-chemical and biological properties with the aim of synthetizing high-performing devices for specific use. In this context, intelligent polymeric devices able to be morphologically modified in response to an internal or external stimulus, such as pH or temperature, have been actively pursued. In general, hydrophilic polymeric materials lead to high in vitro and/or in vivo therapeutic efficacy, with programmed site-specific feature showing remarkable potential for targeted therapy. This Special Issue serves to highlight and capture the contemporary progress in this field. Relevant resources and people to approach - American Association Pharmaceutical Scientists (AAPS): web: www.aaps.org; email: (marketing division): [email protected]; (mmeting division): [email protected] - International Association for Pharmaceutical Technology (APV): web: apv-mainz.de; email (managing director)

Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release

Electrically Controlled Drug Release using Graphene Based Hydrogels

The quest to understand drug delivery to a specific site, quantity, or time has led to various method of trying to control drug delivery. If controllable drug delivery is mastered, managing and treating diseases will improve dramatically. Liposomes, microsomes and hydrogel are currently been used for these purpose. Hydrogels with three dimensional network of hydrophilic polymers are being considered because of their biocompatibility, minimal mechanical irritation, low cost, and ability to crosslink. Electro-responsive hydrogels are now been favored as to others such pH, temperature and light stimulated hydrogel because of the availability of the equipment, precise control on the magnitude of current, intervals and duration of electric pulses. Incorporating graphene in this hydrogel can also in improving drug delivery

pH-responsive nanofibers with controlled drug release properties

Cataloged from PDF version of article.Smart polymers and nanofibers are potentially intriguing materials for controlled release of bioactive agents. This work describes a new class of pH responsive nanofibers for drug delivery systems with controlled release properties. Initially, poly(4-vinylbenzoic acid-co-(ar-vinylbenzyl) trimethylammonium chloride) [poly(VBA-co-VBTAC)] was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Then, ciprofloxacin was chosen as the model drug for the release study and encapsulated into pH-responsive polymeric carriers of poly(VBA-co-VBTAC) nanofibers via electrospinning. The morphology of the electrospun nanofibers was examined by scanning electron microscopy (SEM). The structural characteristics of the pH responsive nanofibers were investigated by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The release measurements of ciprofloxacin from pH responsive nanofibers were also performed by high-performance liquid chromatography (HPLC) analysis. To show the pH sensitivity of these nanofibers, the release profile of ciprofloxacin was examined under acidic, neutral and basic conditions. The results indicate that pH responsive nanofibers can serve as effective drug carriers since the release of ciprofloxacin could be controlled by changing the pH of the environment, and therefore these drug loaded pH-responsive nanofibers might have potential applications in the biomedical field. This journal is © The Royal Society of Chemistry

Two-component supramolecular hydrogel for controlled drug release

A hybrid gel has been developed by combining two supramolecular gelators. Each gelator endows the hybrid gel with its own characteristics. One gelator enables pH-mediated controlled release of the active pharmaceutical ingredient naproxen, while the other new gelator enhances mechanical stability. Self-assembly thus gives multi-functional gels with potential applications