Doaa Ragab

Crystallization of Progesterone for Pulmonary Drug Delivery

The purpose of this study is to investigate the suitability of the crystallization process to produce microcrystals of progesterone for respiratory drug delivery. Crystallization of progesterone was carried out from water-isopropanol (IPA) mixture. The antisolvent (water) was added at two different addition rates (10 and 100 mL/min). The mass percentage of antisolvent was varied between (50% and 75%), and the initial drug concentration was adjusted at (0.5 and 1 g/L). The effect of crystallization method (antisolvent precipitation or combined cooling and antisolvent) was also examined. These operating conditions were investigated in a 2(4) factorial design in an effort to optimize the process. Different solid-state and surface characterization techniques were applied in conjunction with measurements of powder flow properties using aerodynamic particle sizer (APS). Powder dispersibility and aerosol performance were analyzed using Anderson Cascade Impactor (ACI). Antisolvent addition rate, initial drug concentration and dynamic solvent composition are shown to have a significant effect on the aerosol characteristics of progesterone microcrystals. An increase of 38.73% in the fine particle fraction (FPF) was demonstrated for some powders produced by combined cooling and antisolvent crystallization. In conclusion, it was possible to control particle size and hence, pulmonary deposition using process parameters alone, and produce particles with a narrow particle size distribution and a mean particle size of 5 microm with nearly no particles larger than 10 microm by direct crystallization. The suitability of deep pulmonary deposition was proved by the platelet-like morphology of processed microcrystals and greater surface-to-volume ratio than spherical particles.

Controlled release of 5-fluorouracil and progesterone from magnetic nanoaggregates

Background The potential use of magnetic nanoparticles in biomedical applications has witnessed an exponential growth in recent years. Methods In this study, we used nanoaggregates of magnetic nanoparticles as carriers for controlled drug delivery. The nanoaggregates are formed due to the presence of the block copolymer of polyethylene oxide-polypropylene oxide (Pluronic F-68) and beta-cyclodextrin that surround the magnetic core of the nanoparticles. The administration of the drug carriers occurs by inhalation, and the drug is delivered systemically via the pulmonary route. We tested the delivery of 5-fluorouracil and progesterone, which are used as models of hydrophilic and hydrophobic drugs, respectively. Results The estimated nanoaggregates’ diameters are between 293 nm ± 14.65 nm and 90.2 nm ± 4.51 nm, respectively. In-situ and post-synthesis techniques are two approaches for drug loading. The polymer composition of nanoaggregates and initial drug concentration showed a significant effect on both the drug entrapment efficiency and release kinetics. Average drug entrapment efficiencies ranged between 16.11% and 83.25%. In-situ loaded samples showed significantly slower release rates. The drug release mechanism is investigated by mathematical curve fitting to different drug release kinetics models. In most cases, the Peppas model has shown good correlations (coefficients of correlation, R2, between 0.85 and 0.99) with the examined release profiles. The estimated release indices are below 0.5, which indicates the Fickian diffusion mechanism. For samples with an initial burst effect, the modified Peppas model can provide a better understanding of the drug release mechanism, both in the samples loaded with progesterone, or those high polymer concentrations. Conclusion Our work showed prolonged delivery of drugs (5-fluorouracil and progesterone) by diffusion from nanoaggregates, with the potential to reduce dose-related adverse effects.

Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery.

BACKGROUND Engineered magnetic nanoparticles (MNPs) possess unique properties and hold great potential in biomedicine and clinical applications. With their magnetic properties and their ability to work at cellular and molecular level, MNP have been applied both in-vitro and in-vivo in targeted drug delivery and imaging. Focusing on Iron Oxide Superparamagnetic nanoparticles (SPIONs), this paper elaborates on the recent advances in development of hybrid polymeric-magnetic nanoparticles. Their main applications in drug delivery include Chemotherapeutics, Hyperthermia treatment, Radio-therapeutics, Gene delivary, and Biotheraputics. Physiochemical properties such as size, shape, surface and magnetic properties are key factors in determining their behavior. Additionally tailoring SPIONs surface is often vital for desired cell targetting and improved efficiency. Polymer coating is specifically reviewed with brief discussion of SPIONs administration routes. Commonly used drug release models for describing release mechanisms and the nanotoxicity aspects are also discussed. METHODS This review focus on superparamagnetic nanoparticles coated with different types of polymers starting with the key physiochemical features that dominate their behavior. The importance of surface modification is addressed. Subsequently, the major classes of polymer modified iron oxide nanoparticles is demonstrated according to their clinical use and application. Clinically approved nanoparticles are then addressed and the different routes of administration are mentioned. Lastly, mathematical models of drug release profile of the common used nanoparticles are addressed. RESULTS MNPs emerging in recent medicine are remarkable for both imaging and therapeutics, particularly, as drug carriers for their great potential in targeted delivery and cancer treatment. Targeting ability and biocompatibility can be improved though surface coating which provides a mean to alter the surface features including physical characteristics and chemical functionality. The use of biocompatible polymers can prevent aggregation, increase colloidal stability, evades nanoparticles uptake by RES, and can provide a surface for conjugation of targeting ligands such as peptide and biomolecules with high affinity to target cells. CONCLUSION Great efforts to bring MNPs from lab testing stage to clinic are needed to understand their physicochemical properties and how they behave in vivo, which resulted in few of them to exist in the market today. Although magnetic nanoparticles have not yet fully reached their optimal safety and efficiency due to the challenges they face in vivo, their shortcomings can be overcome through improvement of magnetictargeted carrier by pre-clinical trials and continuous studies.

Magnetic Mirtazapine Loaded Poly(propylene glycol)bis(2aminopropylether) (PPG-NH2, MW_2000) Nanocarriers for Controlled Drug Release

Mirtazapine is an antidepressant that was introduced in 1996 for the treatment of moderate and severe depression. Mirtazapine is the only tetracyclic antidepressant that is approved by the Food and Drug Administration to treat depression. Mirtazapine is devoid of most side effects but has antihistamine side effects of drowsiness and weight gain. Its bioavailability is only fifty percent. The low bioavailability and side effects can be improved by altering the pharmokinetic profile of the drug by controlling the release of the drug. The slow release of the drug will reduce the harmful affect it has on the cells decreasing the side effects, as well as the loading of the drug in the nanocarrier will allow for a longer residence time in the body before it is removed by the gastrointestinal tract. In this research paper the pharmokinetic profile of Mirtazapine will be altered by surrounding the drug with a biodegradable polymer called poly(propylene glycol) bis(2-aminopropylether) (PPG-NH2, MW _ 2000) chains. This profile will be done at different polymer concentrations, drug concentrations and solubilizer concentration to see how this will affect the release of the drug. In this research project it was found that using a lower concentration of poly(propylene glycol) bis (2-aminopropylether) (PPG-NH2, MW_2000) chains of 0.5 g/mL led to a slower release in comparison to the other polymer concentrations with an encapsulation of 10 mg of Mirtazapine. When the drug weight was increased but the polymer concentration stayed the same (0.95 g/mL) the release rate increased with drug concentration. Also when the stabilizer concentration was increased, but the polymer concentration and drug concentration remained the same (0.95 g/mL and 10 mg respectively) the release rate increased. Therefore in order to allow for a slower release rate one should use the lower polymer concentration of 0.95 g/mL, with the lower concentration of stabilizer. This will allow for a slower release of the drug Mirtazapine which will lower the side effects and increase the bioavailability percentage.