Kinetics and the Theoretical Aspects of Drug Release from PLA/HAp Thin Films

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The theory of dissolution kinetics of gentamicin from polylactic acid-hydroxyapatite thin film composites is spotlighted with the combination of diffusion and polymer degradation modeling. The use of various mathematical models, characterizing diffusion, dissolution or/and erosion prevalence as well as a mix of dissolution-diffusion rate processes were employed in order to compare theory with experimental data. A number of factors influence the release kinetics of gentamicin from medical drug release systems and devices. It is difficult to have a single mathematical model that takes all these factors into account. It is shown that the degradation of the polymer matrix plays the biggest role in the release kinetics of polymer-ceramics thin film composites. It was also observed that multistage drug release form these devices depends also on the degradation kinetics of the polymer matrix. The effect of pH and device sizes were not studied but could also be of interest in future studies

Conversion of Marine Structures to Calcium Phosphate Materials: Mechanisms of Conversion Using Two Different Phosphate Solutions

Marine structure, coralline materials were converted to calcium phosphate using two different phosphate solutions. The aim was to study the conversion mechanisms under acidic and basic environment at moderate conditions of temperature. Crystal growth and morphology of converted corals were characterized by XRD and SEM respectively. The results suggested that under acidic conditions (H3PO4), dissolution and precipitation control and direct the crystal formation and morphology in which transition from plate like to rod like hydroxyapatite structure was favoured. Metastable phase such as monetite formed and transformed to HAp during reaction. During the first hour of the dissolution a monetite and hydroxyapatite mixture precipitates and then the full conversion to hydroxyapatite is observed. On the other hand, under basic conditions (NH4)2HPO4, just diffusional surface conversion of the calcium carbonate structure of coralline materials to hydroxyapatite and a very small amount of tri-calcium phosphate is observed. The mechanism can be classified as the solid-state topotactic ion-exchange reaction mechanism

Drug Delivery From Polymer-Based Nanopharmaceuticals—An Experimental Study Complemented by Simulations of Selected Diffusion Processes

The success of medical therapy depends on the correct amount and the appropriate delivery of the required drugs for treatment. By using biodegradable polymers a drug delivery over a time span of weeks or even months is made possible. This opens up a variety of strategies for better medication. The drug is embedded in a biodegradable polymer (the “carrier”) and injected in a particular position of the human body. As a consequence of the interplay between the diffusion process and the degrading polymer the drug is released in a controlled manner. In this work we study the controlled release of medication experimentally by measuring the delivered amount of drug within a cylindrical shell over a long time interval into the body fluid. Moreover, a simple continuum model of the Fickean type is initially proposed and solved in closed-form. It is used for simulating some of the observed release processes for this type of carrier and takes the geometry of the drug container explicitly into account. By comparing the measurement data and the model predictions diffusion coefficients are obtained. It turns out that within this simple model the coefficients change over time. This contradicts the idea that diffusion coefficients are constants independent of the considered geometry. The model is therefore extended by taking an additional absorption term into account leading to a concentration dependent diffusion coefficient. This could now be used for further predictions of drug release in carriers of different shape. For a better understanding of the complex diffusion and degradation phenomena the underlying physics is discussed in detail and even more sophisticated models involving different degradation and mass transport phenomena are proposed for future work and study

Antibiotic Containing Poly Lactic Acid/Hydroxyapatite Biocomposite Coatings for Dental Implant Applications

The biodegradable and biocompatible antibiotic containing thin film composites are very appropriate biomaterials as coating materials for dental implants because of their adjustable drug loading and release rates for the prevention of implant related infections. Coralline hydroxyapatite (HAp) was loaded with gentamicin antibiotics and combined with a biodegradable polylactic acid (PLA) to form thin film composites. PLA-HAp, PLA-Gentamicin (GM) and PLA-HAp-GM composites were produced, and their dissolution studies were carried out in phosphate buffered saline under SINK conditions. It was observed that the coatings could be efficiently applied to titanium dental implants and the drug release rates can be efficiently controlled

Comparative study of coral conversion, Part 3: Intermediate products in the first half an hour

Different methods to produce calcium phosphate materials have been well established and are currently used by both scientific and industrial community. While other new and more economical production techniques are under development, the actual reactions mechanisms involve in these techniques are not well understood. Understanding what really happen during reaction will pave a way to tune the final product for well-defined morphology and purity. We focused into improving in-depth understanding of the reaction mechanisms and the intermediates products participating in the reaction of coralline materials with orthophosphoric and ammonium phosphate solutions under mechano-chemical reaction technique. The results suggest that within 30 minutes of reaction under ammonium phosphate solution only HAp phase is produced through solid-state iron exchange reaction. On the other hand, under orthophosphoric acid solution, intermediate phases such as octacalcium phosphate (OCP) and monetite form and convert to hydroxyapatite HAp at different times. Other phase that formed as an intermediate was identified as brushite. It was also observed that pH plays a big role in the formation of these phases due to their different pH stability. The results also confirm our previous hypothesis that under orthophosphoric acid phosphate solution the reaction mechanism is dissolution-recrystallization while under ammonium phosphate solution is solid-state topotactic ion exchange reaction mechanism. It is envisaged that there are possibilities of the formation of intermediate products within or before the first 5 minutes of reaction

In vitro bioactivity and stem cells attachment of three-dimensionally ordered macroporous bioactive glass incorporating iron oxides

Three-dimensionally ordered macroporous bioactive SiO2-CaO-Na2O-P2O5 glass (3DOM-BG) is synthesized by using the sol-gel method. After an in vitro test in simulated body fluid (SBF), the hydroxyapatite (HAp) crystalline phase is clearly formed on its surface as confirmed by X-ray diffractometry (XRD) and Raman spectroscopy. Magnetic 3DOM-BG/Fe samples are synthesized by partial substitution of SiO2 with iron oxide. Whilst the HAp layer is not confirmed, energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and XRD analysis reveal calcium phosphate layer on the surface of 3DOM-BG/Fe samples after the SBF soaking. The growth of HAp-like layer is slower with increasing iron oxides. The initial mechanism that thought to induce bone formation is reduced due to the replacement of Ca2+ with Fe ions in the glass network. The formation of HAp-like layer is modified by the sedimentation of Ca and P while the nonmagnetic 3DOM-BG forms the calcium phosphate by the ionic exchange following the Hench mechanism. The adult human adipose tissue-derived stem cells (hADSCs) can be closely attached and well spread on the flat-plate of all 3DOM-BG/Fe and 3DOM-BG. Without detectable cytotoxicity possibly induced by iron oxides, the osteoblast can be grown and proliferated. In addition to these bioactivity and biocompatibility, porous structures can allow their possible use in targeted drug delivery and magnetic properties of 3DOM-BG/Fe can essentially be implemented in hyperthermia therapy

Comparative Study of Conversion of Coral with Ammonium Dihydrogen Phosphate and Orthophosphoric Acid to Produce Calcium Phosphates

address significant advantages due to their unique structures and chemical compositions that contain Mg and Sr. Many conversion processes has been in the past proposed. In this work, a comparison study between the conversion of coral with orthophosphoric acid and ammonium dihydrogen phosphate was conducted. The resultant structures and compositions were studied using XRD, ICP-MS, SEM and FTIR. The results show that with phosphoric acid the coral was converted into mainly monetite (92%). The ammonium dihydrogen phosphate converted approximately 76% of the coral to hydroxyapatite through solid state reactions. The two routes proved to be effective in producing bioceramic materials from corals under moderate conditions of temperature with a basic condition favouring the yield of hydroxyapatite

Calcium phosphate and bioglass reinforced PLA thin film biocomposites for slow drug delivery applications

University of Technology Sydney. Faculty of Science.The rise in the number of musculoskeletal disorders (MSDs) due to the increase in aging population and advancement in medical technology has led to an increasing demand for medication to prevent and treat these diseases. The development of new drugs or formulations to allow treatment of these diseases in their very early stages is only increasing. Local direct and multidelivery of medication and key minerals to support bone repair and regeneration at the defect site, from flexible degradable devices at the rate within the therapeutic window, seems to be an effective strategy. However current drug delivery vehicles are neither flexible and degradable, nor able to deliver both medication and minerals effectively. Using a simple “solution casting” method, preparation of medical devices with such potential for slow drug delivery for biomedical applications served as the research objective. Polylactic acid (PLA) and hydroxyapatite-hydrothermally converted coral were used to develop PLA thin film composites as drug delivery systems. PLA provided flexibility and biodegradability of the systems, while coralline hydroxyapatite provided a unique architecture with its porous and bioactive nature, which is suitable for drug loading and slow drug release. Two drugs, gentamicin (antibiotic) and bisphosphonate were loaded into the device and their release profiles and activities were studied for the treatment of medical-implant related infection and osteoposis respectively. The biocompatibility study on human adipose derived stem cells (hADSC) and biofilm formation behaviour of both gram-negative (Pseudomonas aeruginosa) and gram-positive bacterial (Staphylococcus aureus) were studied on PLA thin film composites loaded with gentamicin. The mechanical properties of PLA-surface treated bioglass for tissue engineering applications was also studied. An alternative conversion method of coralline materials and other natural materials such as sea mussel and ostrich eggshells to calcium phosphate materials were also evaluated. Although nanosurface bioglass treated with 1% (3-Aminopropyl) triethoxysilane (APTES) suggested effective improvement in elongation at the break of PLA/bioglass composites, they lacked the required drug release efficiency. However, the PLA thin film composites displayed ability for potential applications in biomedical field as drug delivery systems. The flexibility they provide allows them to conform to any desired clinical shape and size. Incorporation of hydroxyapatite in the matrix, has the added advantages of controlled release, improved encapsulation efficiency, increased drug stability and maintenance of bioactivity and continuous supply of calcium Ca²⁺ and phosphate PO₄²⁻ ions, which can assist in bone regeneration and repair. Gentamicin release profiles, exhibited a steady state release rate, with significant antimicrobial activity even at high concentrations of bacteria. The systems also showed the potential for prolonged release of both antibiotic and bisphosphonate. The loading of the drug onto HAp particles induces a significant decrease of the release rate and period, for both gentamicin and bisphosphonate permitting the therapeutic efficacy of composite biomaterial locally to be extended. hADSC showed attachment and proliferation on PLA thin film-HAp composites signifying the increase in osteointegration due to the presence of HAp. Mechano-chemical conversion methods proved to be an effective alternative to the hydrothermal technique for coral conversion to calcium phosphate materials at moderate temperature conditions. The modified composites may have a wide range of biomedical applications in tissue engineering with improved elastic properties

Pesticide safety practice and its determinants among small scale vegetables farmers in Eyasi area, Arusha region Tanzania

Background: Strategies to achieve the millennium agricultural development goals include increased use of pesticides to increase agricultural production in poor countries. However, the increased availability and use of such chemicals need to be paralleled with national and personal level practices to maximize safety for communities and environment.Aim and methods: The aim of this study was to determine the pesticide safety practices among rural farmers in Karatu District in Northern Tanzania. Farmers practicing horticulture farming in Mang’ola Division were interviewed about their practices during and after pesticides application.Results: The study included 148 farmers of whom 79.7% were male. A significantly high proportion (77.7%) of the farmers did not use protective gear while applying pesticides. A notable percentage ate while applying pesticides (17.6%), one out of five took fluids and about a quarter smoked cigarettes. Factors found to be significantly associated with those practices were education, marital status, reporting frequent household spraying, long duration since starting to apply pesticides and farm size (p<0.05).Conclusions: Given the lack of protective behavior, it is then very important that farmers and farm workers are reminded of the hazardous nature of pesticides and the need to have their health monitored regularly. Special educational and information strategies have to focus on those with low education, who are unmarried, working on large farms and have a high frequency of applying pesticides. To enhance sustained education and supervisions, community level surveillance and supervisors could be introduced