Preparation and in vitro release of zein microparticles loaded with prednisolone for oral delivery

Zein has been proposed as a polymer for targeted-drug delivery via the oral route. Zein microparticles were loaded with prednisolone and evaluated as an oral delivery system. Microparticles were formulated using phase separation. Starting quantities of zein and prednisolone, along with the agitation method and temperature were found to significantly impact drug loading and loading efficiency. Vortex mixing produced the highest drug loading and loading efficiency. Drug release was measured in simulated conditions of the stomach and small intestine using the microparticles made with the method that best improved drug loading. In simulated stomach and small intestine conditions, prednisolone release reached almost 70 over 3 and 4h, respectively. While a clinically relevant dose may be delivered using c. 100mg of zein microparticles, prednisolone release from the microparticles indicates that they may not be suited as a controlled-or targeted-delivery system.

Intravitreal drug delivery in retinal disease : are we out of our depth?

Introduction With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise. Areas covered We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally. Expert opinion Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully; however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.

Synthesis and toxicological evaluation of a chitosan‑L‑leucine conjugate for pulmonary drug delivery applications

Herein are reported the synthesis of a conjugate of chitosan with L-leucine, the preparation of nanoparticles from both chitosan and the conjugate for use in pulmonary drug delivery, and the in vitro evaluation of toxicity and inflammatory effects of both the polymers and their nanoparticles on the bronchial epithelial cell line, BEAS-2B. The nanoparticles, successfully prepared both from chitosan and the conjugate, had a diameter in the range of 10−30 nm. The polymers and their nanoparticles were tested for their effects on cell viability by MTT assay, on trans-epithelial permeability by using sodium fluorescein as a fluid phase marker, and on IL-8 secretion by ELISA. The conjugate nanoparticles had a low overall toxicity (IC50 = 2 mg/mL following 48 h exposure; no induction of IL-8 release at 0.5 mg/mL concentration), suggesting that they may be safe for pulmonary drug delivery applications.

Imaging tumour distribution of a polymeric drug delivery platformin vivoby PET-MRI

Background Over the past decade, molecular imaging has played a key role in the progression of drug delivery platforms from concept to commercialisation. Of the molecular imaging techniques commonly utilised, positron emission tomography (PET) can yield a breadth of information not easily accessible by other methodologies and when combined with other complementary imaging modalities, is a powerful tool for pre- and clinical development of therapeutics. However, very little research has focussed on the information available from complimentary imaging modalities. This paper reports on the data-rich methodologies of contrast enhanced PET/CT and PET/MRI for probing efficacy of polymer drug delivery platforms. Results The information available from an ExiTron nano 6000 contrast enhanced PET/CT and a gadolinium (Gd) enhanced PET/MRI image of a 64Cu labeled HBP in the same mouse was qualitatively compared. Conclusions Gd contrast enhanced PET/MRI offers a powerful methodology for investigating the distribution of polymer drug delivery platforms in vivo and throughout a tumour volume. Furthermore, information about depth of penetration away from primary blood vessels can be gleaned, potentially leading to development of more efficacious delivery vehicles for clinical use.

Characterization of Ion-Exchange Fibers for Controlled Drug Delivery

Increasing attention has been focused on methods that deliver pharmacologically active compounds (e.g. drugs, peptides and proteins) in a controlled fashion, so that constant, sustained, site-specific or pulsatile action can be attained. Ion-exchange resins have been widely studied in medical and pharmaceutical applications, including controlled drug delivery, leading to commercialisation of some resin based formulations. Ion-exchangers provide an efficient means to adjust and control drug delivery, as the electrostatic interactions enable precise control of the ion-exchange process and, thus, a more uniform and accurate control of drug release compared to systems that are based only on physical interactions. Unlike the resins, only few studies have been reported on ion-exchange fibers in drug delivery. However, the ion-exchange fibers have many advantageous properties compared to the conventional ion-exchange resins, such as more efficient compound loading into and release from the ion-exchanger, easier incorporation of drug-sized compounds, enhanced control of the ion-exchange process, better mechanical, chemical and thermal stability, and good formulation properties, which make the fibers attractive materials for controlled drug delivery systems. In this study, the factors affecting the nature and strength of the binding/loading of drug-sized model compounds into the ion-exchange fibers was evaluated comprehensively and, moreover, the controllability of subsequent drug release/delivery from the fibers was assessed by modifying the conditions of external solutions. Also the feasibility of ion-exchange fibers for simultaneous delivery of two drugs in combination was studied by dual loading. Donnan theory and theoretical modelling were applied to gain mechanistic understanding on these factors. The experimental results imply that incorporation of model compounds into the ion-exchange fibers was attained mainly as a result of ionic bonding, with additional contribution of non-specific interactions. Increasing the ion-exchange capacity of the fiber or decreasing the valence of loaded compounds increased the molar loading, while more efficient release of the compounds was observed consistently at conditions where the valence or concentration of the extracting counter-ion was increased. Donnan theory was capable of fully interpreting the ion-exchange equilibria and the theoretical modelling supported precisely the experimental observations. The physico-chemical characteristics (lipophilicity, hydrogen bonding ability) of the model compounds and the framework of the fibrous ion-exchanger influenced the affinity of the drugs towards the fibers and may, thus, affect both drug loading and release. It was concluded that precisely controlled drug delivery may be tailored for each compound, in particularly, by choosing a suitable ion-exchange fiber and optimizing the delivery system to take into account the external conditions, also when delivering two drugs simultaneously.

External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Formulation and characterization of drug-loaded microparticles using distillers dried grain kafirin

Kafirin, a protein extracted from sorghum grain, has been formulated into microparticles and proposed for use as a delivery system owing to the resistance of kafirin to upper gastrointestinal digestion. However, extracting kafirin from sorghum distillers dried grains with solubles (DDGS) may be more efficient, because the carbohydrate component has been removed by fermentation. This study investigated the properties and use of kafirin extracted from DDGS to formulate microparticles. Prednisolone, an anti-inflammatory drug that could benefit from a delayed and targeted delivery system to the colon, was loaded into DDGS kafirin microparticles by phase separation with sodium chloride. Scanning electron micrographs revealed that the empty and prednisolone-loaded microparticles were round in shape and varied in size. Surface binding studies indicated prednisolone was loaded within the microparticles rather than being solely bound on the surface. These findings demonstrate DDGS kafirin can be formulated into microparticles and loaded with medication. Future studies could investigate the potential applications of DDGS kafirin microparticles as an orally administered targeted drug-delivery system.

Formulation and characterization of drug-loaded microparticles using distiller’s dried grain kafirin

Kafirin, a protein extracted from sorghum grain has been formulated into microparticles, and proposed for use as a delivery system due to the resistance of kafirin to upper gastrointestinal digestion. However, extracting kafirin from sorghum “distiller’s dried grains with solubles” (DDGS) may be more efficient as the carbohydrate component has been removed by fermentation. This study investigated the properties and use of kafirin extracted from DDGS to formulate microparticles. Prednisolone, an anti-inflammatory drug that could benefit from a delayed and targeted delivery system to the colon, was loaded into DDGS kafirin microparticles by phase separation using sodium chloride. Scanning electron micrographs revealed that the empty and prednisolone-loaded microparticles were round in shape and varied in size. Surface binding studies indicated prednisolone was loaded within the microparticles rather than being solely bound on the surface. These findings demonstrate DDGS kafirin can be formulated into microparticles and loaded with medication. Future studies could investigate the potential applications of DDGS kafirin microparticles as an orally administered targeted drug-delivery system.

Formulation and characterization of drug-loaded microparticles using distiller’s dried grain kafirin

Kafirin, a protein extracted from sorghum grain has been formulated into microparticles, and proposed for use as a delivery system due to the resistance of kafirin to upper gastrointestinal digestion. However, extracting kafirin from sorghum distillers dried grains with solubles (DDGS) may be more efficient as the carbohydrate component has been removed by fermentation. This study investigated the properties and use of kafirin extracted from DDGS to formulate microparticles. Prednisolone, an anti-inflammatory drug that could benefit from a delayed and targeted delivery system to the colon, was loaded into DDGS kafirin microparticles by phase separation using sodium chloride. Scanning electron micrographs revealed that the empty and prednisolone-loaded microparticles were round in shape and varied in size. Surface binding studies indicated prednisolone was loaded within the microparticles rather than being solely bound on the surface. These findings demonstrate DDGS kafirin can be formulated into microparticles and loaded with medication. Future studies could investigate the potential applications of DDGS kafirin microparticles as an orally administered targeted drug-delivery system.

Dual Drug Delivery Microcapsules via Layer-by-Layer Self-Assembly

The integration of hydrophobic and hydrophilic drugs in the polymer microcapsule offers the possibility of developing a new drug delivery system that combines the best features of these two distinct classes of material. Recently, we have reported the encapsulation of an uncharged water-insoluble drug in the polymer membrane. The hydrophobic drug is deposited using a layer-by-layer (LbL) technique, which is based on the sequential adsorption of oppositely charged polyelectrolytes onto a charged substrate. In this paper, we report the encapsulation of two different drugs, which are invariably different in structure and in their solubility in water. We have characterized these dual drug vehicular capsules by confocal laser scanning microscopy, atomic force microscopy, visible microscopy, and transmission electron microscopy. The growth of a thin film on a flat substrate by LbL was monitored by UV−vis spectra. The desorption kinetics of two drugs from the thin film was modeled by a second-order rate model.