A Note on the Trandermal Delivery of Clenbuterol

A modified diffusion/compartmental model has been used to simulate the transdermal uptake of clenbuterol from a matrix-type delivery device. The application of a fresh device every 7 days was found to produce a pseudo-steady state drug plasma profile after approx. three changes of device. Of the matrix properties, only drug loading had substantial effect on the drug plasma profile

Mathematical Modelling of Variable Porosity Coatings for Dual Drug Delivery

In this paper we describe a theoretical mathematical model of dual drug delivery from a durable polymer coated medical device. We demonstrate how the release rate of each drug may in principle be controlled by altering the initial loading configuration of the two drugs. By varying the underlying microstructure of polymer coating, further control may be obtained, providing the opportunity to tailor the release profile of each drug for the given application

Curcumin-loaded zeolite as anticancer drug carrier: Effect of curcumin adsorption on zeolite structure

In this work we used a combination of different techniques to investigate the adsorption properties of curcumin by zeolite type A for potential use as an anticancer drug carrier. Curcumin is a natural water-insoluble drug that has attracted great attention in recent years due to its potential anticancer effect in suppressing many types of cancers, while showing a synergistic antitumor effect with other anticancer agents. However, curcumin is poorly soluble in aqueous solutions leading to the application of high drug dosage in oral formulations. Zeolites, inorganic crystalline aluminosilicates with porous structure on the nano- and micro-scale and high internal surface area, can be useful as pharmaceutical carrier systems to encapsulate drugs with intrinsic low aqueous solubility and improve their dissolution. Here, we explore the use of zeolite type A for encapsulation of curcumin, and we investigate its surface properties and morphology, before and after loading of the anticancer agent, using scanning electron microscopy (SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and UV-vis spectroscopy. Results are used to assess the loading efficiency of zeolite type A towards curcumin and its structural stability after loading

Validation of Smart Nanoparticles as Controlled Drug Delivery Systems: Loading and pH-Dependent Release of Pilocarpine

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%- DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.Ministerio de Economía y Competitividad de España-MAT2016-77345-C3-2-PJunta de Andalucía-P12-FQM-155

Ligation of anti-cancer drugs to self-assembling ultrashort peptides by click chemistry for localized therapy

Self-assembling ultrashort peptides from aliphatic amino acids were functionalized with platinum anti-cancer drugs by click chemistry. Oxaliplatin-derived hybrid peptide hydrogels with up to 40% drug loading were tested for localized breast cancer therapy. Stably injected gels showed significant tumor growth inhibition in mice and a better tolerance compared to the free platinum drug

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

Validation of smart nanoparticles as controlled drug delivery systems: loading and pH-dependent release of pilocarpine

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.Peer ReviewedPostprint (published version

A novel multifunctional biomedical material based on polyacrylonitrile:preparation and characterization

Wet spun microfibers have great potential in the design of multifunctional controlled release materials. Curcumin (Cur) and vitamin E acetate (Vit. E Ac) were used as a model drug system to evaluate the potential application of the drug-loaded microfiber system for enhanced delivery. The drugs and polyacrylonitrile (PAN) were blended together and spun to produce the target drug-loaded microfiber using an improved wet-spinning method and then the microfibers were successfully woven into fabrics. Morphological, mechanical properties, thermal behavior, drug release performance characteristics, and cytocompatibility were determined. The drug-loaded microfiber had a lobed “kidney” shape with a height of 50 ~ 100 μm and width of 100 ~ 200 μm. The addition of Cur and Vit. E Ac had a great influence on the surface and cross section structure of the microfiber, leading to a rough surface having microvoids. X-ray diffraction and Fourier transform infrared spectroscopy indicated that the drugs were successfully encapsulated and dispersed evenly in the microfilament fiber. After drug loading, the mechanical performance of the microfilament changed, with the breaking strength improved slightly, but the tensile elongation increased significantly. Thermogravimetric results showed that the drug load had no apparent adverse effect on the thermal properties of the microfibers. However, drug release from the fiber, as determined through in-vitro experiments, is relatively low and this property is maintained over time. Furthermore, in-vitro cytocompatibility testing showed that no cytotoxicty on the L929 cells was found up to 5% and 10% respectively of the theoretical drug loading content (TDLC) of curcumin and vitamin E acetate. This study provides reference data to aid the development of multifunctional textiles and to explore their use in the biomedical material field

Picoliter-volume inkjet printing into planar microdevice reservoirs for low-waste, high-capacity drug loading.

Oral delivery of therapeutics is the preferred route for systemic drug administration due to ease of access and improved patient compliance. However, many therapeutics suffer from low oral bioavailability due to low pH and enzymatic conditions, poor cellular permeability, and low residence time. Microfabrication techniques have been used to create planar, asymmetric microdevices for oral drug delivery to address these limitations. The geometry of these microdevices facilitates prolonged drug exposure with unidirectional release of drug toward gastrointestinal epithelium. While these devices have significantly enhanced drug permeability in vitro and in vivo, loading drug into the micron-scale reservoirs of the devices in a low-waste, high-capacity manner remains challenging. Here, we use picoliter-volume inkjet printing to load topotecan and insulin into planar microdevices efficiently. Following a simple surface functionalization step, drug solution can be spotted into the microdevice reservoir. We show that relatively high capacities of both topotecan and insulin can be loaded into microdevices in a rapid, automated process with little to no drug waste

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