Richard T. Addo

Formulation and Characterization of Atropine Sulfate in Albumin–Chitosan Microparticles for In Vivo Ocular Drug Delivery

The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions

Formulation and characterization of catalase in albumin microspheres.

Abstract Catalase in albumin microspheres were formulated for intravenous administration to antagonize the effects of over-production of reactive oxygenated species (ROS) such as hydrogen peroxide (H2O2) in septic shock. The aim was to increase effective half-life of catalase and take advantage of the phagocytic uptake of the encapsulated catalase by the vascular endothelium. Catalase microspheres were prepared by spray-drying. The microspheres were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy (SEM), drug encapsulation efficiency, chemical stability, thermal stability and in vitro drug release characteristics. The microspheres had a mean particle size of 4.7 ± 2 µm, optimal for phagocytic uptake, as demonstrated by Makino et al. SEM revealed that microspheres were spherical with smooth surface morphology. An encapsulation efficiency of 91.5 ± 3% was achieved and the encapsulated catalase was chemically and thermally stable. Application of in vitro drug release data to the Higuchi kinetic equation indicated matrix diffusion-controlled catalase release from albumin microspheres.

Spray-dried doxorubicin-albumin microparticulate systems for treatment of multidrug resistant melanomas

As multidrug resistance continues to be a problem in cancer treatment, controlled release delivery systems, such as microspheres, may aid to give a slower release of anticancer drugs into drug resistant tumor cells. In this study doxorubicin microspheres microencapsulated in an albumin matrix were prepared via the spray-drying method and characterized for particle size, content analysis, and release studies. They were then evaluated in vitro using drug resistant murine melanoma tumor cells for uptake and efflux studies. Spray-drying produced a dispersed powder with a mean particle size of 4.91 ± 1.2 µm, 60% product yield, and encapsulation efficiency of 85% and a ζ potential range of 37 to −40 mV. Intracellular doxorubicin concentrations were higher in drug resistant tumor cells treated with microspheres as opposed to solution, and efflux of doxorubicin from the tumor cell was inhibited. Greater cytotoxic effects were seen in tumor cells treated with doxorubicin microspheres versus solution up to and after 3 days. In vivo pharmacokinetic studies conducted in male Sprague–Dawley rats, revealed a plasma-level time curve indicative of a two-compartment model, and showed prolonged half-life of doxorubicin, greater area under the plasma concentration time curve, and increased plasma concentrations of doxorubicin in rats at 8 and 24 h after administration of doxorubicin microspheres.

Treatment of adjuvant arthritis using microencapsulated antisense NF-κB oligonucleotides

Antisense oligonucleotides are promising new therapeutic agents used to selectively inhibit target genes such as Nuclear Factor Kappa B (NF-κB), an important transcription factor in the pathogenesis of inflammatory disease. The purpose of the present study was to evaluate microencapsulated antisense oligonucleotides specific to NF-κB for in vitro efficacy and treatment of adjuvant-induced arthritis in rats. Oligonucleotide-loaded albumin microspheres were prepared and characterized in terms of size, zeta potential, morphology and release pattern. This study reports significant NF-κB inhibition in vitro after treatment with microencapsulated antisense oligonucleotides. Furthermore, microencapsulated antisense NF-κB oligonucleotides were found to inhibit paw inflammation associated with rat adjuvant-induced arthritis in a dose-dependent manner. Taken together, the results presented in this work described albumin microspheres to be effective delivery vehicles for antisense NF-κB oligonucleotides and a potential treatment for inflammatory diseases.

Emerging advances in cancer nanotheranostics with graphene nanocomposites: opportunities and challenges

As an inorganic nanomaterial, graphene nanocomposites have gained much attention in cancer nanotechnology compared with the other inorganic nanomaterial in recent times. Although a relatively new drug carrier, it has been extensively explored as a potential chemotherapeutic carrier and theranostic because of its numerous physicochemical properties, including, capability of multiple pay load, functionalization for drug targeting and photothermal effect. Despite potential benefit, its translation from bench to bed-side in cancer therapy is challenged due to its toxicity concern. Here, we discussed the present progress and future possibilities of graphene nanocomposites as a cancer theranostic. Moreover, the paper also exemplifies the effects of graphene/graphene oxide on tissues and organ functions in order to understand the extent and mechanism of toxicity.

Development and Validation of a UPLC Method for Rapid and Simultaneous Analysis of Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are used extensively for the relief of gastroesophageal reflux, peptic ulcers, and other hypersecretory conditions. Some of the commonly used PPIs—omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole—were used in this study with the aim of developing a rapid ultra performance liquid chromatography (UPLC) method for detecting each and allowing separation and quantification of a mixture of PPIs. An analysis of samples was performed on a UPLC system equipped with a quaternary solvent delivery system, a refrigerated sample manager, a column heater, a photo diode array detector scanning from 210 to 400 nm, and a C18 analytical column (50 mm × 3.0 mm, 1.7-μm particle size). The chromatographic analysis of the PPI samples and standards was performed using gradient elution with acetonitrile and water. The calibration curve range varied for each of the PPIs ranging from a lower limit of 0.75–1.78 μg/mL to a maximum concentration of 200 μg/mL with a regression coefficient (r2) of ≥0.98. The accuracy and precision were calculated, and the %RSD was determined to be ≤0.21% (intraday) and ≤5% (interday). The LOD was 0.23–0.59 μg/mL and the LOQ was 0.71–1.78 μg/mL for each of the drugs analyzed. The method was capable of detecting and quantifying each drug in a mixture with good resolution and a total run time of less than 5 min. Herein, we report an efficient and rapid analytical method for the simultaneous detection of multiple PPIs in a mixture.

In vitro and ex vivo characterization of lectin-labeled Mycobacterium tuberculosis antigen-containing microspheres for enhanced oral delivery

Abstract Purpose: Oral immunization for mucosal protection against Mycobacterium tuberculosis would be the best option for effective tuberculosis (TB) control. However, this route of vaccine delivery is limited due to the short residence time of the delivery system at the site of absorption. Cytoadhension has made it possible to optimize the targeted delivery of oral vaccine to lymphoid tissues. The purpose of this project was to evaluate the ability of human M-cell specific lectin-labeled microparticles to target the human M-cells of the Peyer’s patches. Method: Albumin microspheres containing Mycobacterium tuberculosis cell lysate antigens were coupled with Wheat germ agglutinin and Aleuria aurantia lectins and their ability to bind to M cell models as well as their preferential distribution in the Peyer’s patches were investigated. Results: The study demonstrated an enhanced delivery of targeted polystyrene and BSA/Lysate microspheres to M cells. It was demonstrated that alpha-l-fucose sugar residue might be the target of these lectins. Conclusion: It can be concluded from the study that the lectin-coupled microspheres had better affinity for M-cells and showed preferential binding to the Peyer’s patches. This means that the coupling enhanced the targeted delivery of the antigens to the M cells.

Pharmacy Student Performance on Constructed-Response Versus Selected-Response Calculations Questions

Objective. To introduce PharmD students to changes in calculations question types (constructed-response versus selected-response questions); measure and compare student performance on constructed-response and selected-response questions in a pharmaceutics course; and collect student feedback on the use of differing question types. Methods A pharmaceutics/pharmaceutical calculations examination was administered that included 15 pairs of questions; each pair consisted of a constructed-response question and a similar selected-response question. An online questionnaire was conducted to collect student feedback. Results. Of the 15 topics, the class scored higher on the constructed-response question for 4 topics and higher on the selected-response question for 10 topics. Eighty percent of the class preferred selected-response questions, although 47.8% felt constructed-response questions better prepared them for a career in healthcare. Conclusions. Students correctly answered more selected-response questions than constructed-response questions and felt more confident in doing so. Additional constructed-response teaching and testing methods should be incorporated into pharmacy education.

The effect of antisense to NF-κB in an albumin microsphere formulation on the progression of left-ventricular remodeling associated with chronic volume overload in rats

Abstract Background: Increased NF-κB levels play a crucial role in the pathophysiology of heart failure and are known to cause ventricular remodeling. Antisense therapy can be used for blocking the expression of NF-κB and subsequently avoiding heart failure. However, as with most biotechnology products, molecular instability and overall cost are often the major issues and concerns limiting the advancement of most antisense drugs to the market. Therefore, a cost-efficient biodegradable sustained release particle drug delivery system to transport and target NF-kB antisense to its intended site of action would be ideal. Purpose: To evaluate the in vivo performance of a sustained release spray-dried albumin microsphere formulation for effective delivery and treatment of left ventricular remodeling with antisense to NF-κB. Methods: Albumin-based microspheres encapsulating antisense to NF-kB were prepared by spray drying and studied in a rat model to treat congestive heart failure. Results: The NF-κB activation and TNF-α release seen in treated animals were significantly lower than control animals. Ventricular remodeling was controlled in animals with antisense-treated AV fistulas as ΔV0–25 and ΔV0 were significantly lower compared to animals with untreated AV fistulas. Conclusion: This treatment was successful in curbing ventricular remodeling by suppressing NF-κB activation.

Nanotechnology for Transcorneal Drug Targeting in Glaucoma: Challenges and Progress

The eye is a highly protected organ, and designing ocular formulation for effective therapy, is challenging for drug delivery researcher. The anatomical and physiological barriers resulted in a low ocular bioavailability of administered drugs. Poor bioavailability of ocularly administered drugs is mainly due to factors responsible for precorneal loss (like tear dynamics, non-productive absorption, a transient residence time in the cul-de-sac, and relative impermeability of the corneal epithelial membrane). Due to these constraints, less than 5 % of the administered dose is absorbed from the conventional ophthalmic dosage forms. Vision-threatening diseases like glaucoma alter the physiology and molecular mechanism of vision. Ocular drug delivery in this dreadful condition is quite challenging. Though, the potential use of a nanoparticulate system as drug carriers has led to the development of many different colloidal delivery vehicles for targeted delivery in glaucoma. Drug loaded colloidal carriers associated with several favorable biological characteristics such as biodegradability, biocompatibility and mucoadhesiveness have been found to be effective in transcorneal drug targeting in glaucoma. These nanoparticulate systems exhibited better ocular drug efficacy by improving ocular bioavailability without blurring the vision in glaucoma. This chapter aims to briefly discuss the ocular barriers to glaucoma drug delivery along with nanotechnology mediated transcorneal drug targeting.