Research Repository :: Browsing by Author "Cazalbou, Sophie"

Browsing by Author "Cazalbou, Sophie"

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Antibiotic Containing Poly Lactic Acid/Hydroxyapatite Biocomposite Coatings for Dental Implant Applications
(Trans Tech Publications Inc, 2017-11) Karacan, Ipek; Macha, Innocent J; Choi, Gina; Cazalbou, Sophie; Ben-Nissan, Besim
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.
Biocompatibility of a new biodegradable polymer-hydroxyapatite composite for biomedical applications
(Elservier, 2017-04) Macha, Innocent J; Ben-Nissan, Besim; Santos, Jerran; Cazalbou, Sophie; Stamboulis, Artemis; Grossin, David; Giordano, Gerard
The rise in the number of musculoskeletal disorders (MSDs) due to an increasingly aging population has led to a growing demand for medication to prevent and treat these diseases. An increased interest in the development of new drugs to allow treatment of these diseases in their very early stages is currently observed. The current approach on local direct delivery of medication and key minerals to support bone repair and regeneration at the defect site, from flexible degradable devices, seems to be an effective strategy. Polylactic acid (PLA) and microspheres of hydrothermally converted coralline hydroxyapatite (cHAp) were used to develop PLA thin film composites as drug delivery systems. The PLA provided flexibility and biodegradability of the systems, while coralline hydroxyapatite provided the required calcium and phosphate ions for bone regeneration. These coralline hydroxyapatite microspheres have a unique architecture of interconnected porosity, are bioactive in nature and suitable for drug loading and controlled slow drug release. The cell attachment and morphology of the PLA thin film composites were evaluated in vitro using cell cultures of human adipose derived stem cells (hADSC). It was shown that hADSC cells exhibited a strong attachment and proliferation on PLA thin film-cHAp composites, signifying high biocompatibility and a potential for osteointegration due to the presence of HAp.
Calcium phosphate nanocoatings and nanocomposites, part 2: thin films for slow drug delivery and osteomyelitis
(Future Medicine, 2016-02-19) Ben-Nissan, Besim; Macha, Innocent J; Cazalbou, Sophie; Choi, Andy H.
During the last two decades although many calcium phosphate based nanomaterials have been proposed for both drug delivery, and bone regeneration, their coating applications have been somehow slow due to the problems related to their complicated synthesis methods. In order to control the efficiency of local drug delivery of a biomaterial the critical pore sizes as well as good control of the chemical composition is pertinent. A variety of calcium phosphate based nanocoated composite drug delivery systems are currently being investigated. This review aims to give an update into the advancements of calcium phosphate nanocoatings and thin film nanolaminates. In particular recent research on PLA/hydroxyapatite composite thin films and coatings into the slow drug delivery for the possible treatment of osteomyelitis is covered.
Comparative study of Coral Conversion, Part 2: Microstructural evolution of calcium phosphate
(Springer NATURE, 2015-06) Macha, Innocent J; Boonyang, Upsorn; Cazalbou, Sophie; Ben-Nissan, Besim; Charvillat, Cédric; Oktar, Faik N; Grossin, David
Calcium phosphate materials can be easily produced by a number of wet chemical methods that involve both acidic and basic environments. In our previous study, we investigated calcium phosphates such as monetite (DCPA), hydroxyapatite (HAp) and whitlockite which were successfully produced by mechano-chemical method from corals obtained from the Great Barrier Reef. It was observed that a number of synthesis factors such as the pH of the environment, the reaction temperature and the chemistry influenced the crystal size formed. A number of theories have been suggested on the mechanisms of crystal formation; however, very few mechanisms have been universally accepted. The present work was aimed to explore the evolution of crystalline calcium phosphate and their morphology with respect to the pH of the environment and reaction time. Conversion of coral to calcium phosphates was carried out with stoichiometric amount of required H3PO4 or (NH4)2HPO4, to obtain hydroxyapatite or tricalcium phosphate (TCP) phases. The acidic or basic solution was added, drop wise, at a rate of 2 mL min-1, to 6 g of coral powder suspended in 300 mL of distilled water at 80 ± 0.5°C on a hot plate with magnetic stirrer. The pH of reaction was monitored. Crystal morphology and the phases were identified by XRD, FTIR, and SEM studies. It was observed that under acidic conditions (H3PO4), dissolution and then precipitation influences the crystal morphology and transition from plate like to rod like hydroxyapatite structure. During the first hour of the dissolution a monetite and hydroxyapatite mixture precipitates and then the full conversion to hydroxyapatite is observed. However under basic conditions (NH4)2HPO4), pH is only marginally changed within the environment and just surface conversion of the calcium carbonate structure of coral 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.
Comparative Study of Coral Conversion, Part 3: Intermediate Products in the First Half an Hour
(2015-12) Macha, Innocent J; Charvillat, Cédric; Cazalbou, Sophie; Grossin, David; Boonyang, Upsorn; Ben-Nissan, Besim
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 fir
Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite–polylactic acid biocomposites for slow drug delivery
(2015-07-15) Macha, Innocent J; Cazalbou, Sophie; Shimmon, Ronald; Ben-Nissan, Besim; Milthorpe, Bruce
An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca2+, in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA–BP and PLA–HAp–BP systems seemed to follow the power law model described by Korsmeyer–Peppas. Drug release was quantified by 31P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca2+ and phosphate ions that can help in bone mineralization.
Development and In Vitro Analysis of a New Biodegradable PLA/Hydroxyapatite (HAp) Composite for Biomedical Applications
(2017-06-08) Macha, Innocent J; Ben-Nissan, Besim; Choi, Andy H.; Cazalbou, Sophie
The development of new drugs or formulations for the treatments of different musculoskeletal disorders (MSDs) has now being a focus of pharmaceutical and scientific societies. Targeted and multidelivery of drug and key minerals to support bone repair and regeneration at the defect site, from flexible biodegradable devices at the rate within the therapeutic window, seem to be an effective strategy. However, the drug delivery vehicles available are neither flexible and degradable nor able to deliver both pharmaceutical drug and minerals effectively. The use of biodegradable polymer and bioceramic for composite development with enough flexibility and potential for slow in situ drug delivery for biomedical applications could be one of the real options to mitigate MSDs problem. In vitro analysis of the developed devices is a vital step towards clinical trial and commercialization of the implant. Different approach and results have been compared to draw guidelines for the development and testing of thin film composite applications as a slow drug delivery vehicle.
Development of antimicrobial composite coatings for drug release in dental, orthopaedic and neural prostheses applications
(Springer NATURE, 2019-01) Macha, Innocent J; Karacan, Ipek; Ben-Nissan, Besim; Cazalbou, Sophie; Muller, Wolfgang H
While one of the major clinical and scientific challenges in the management of implant-related infections and post- operative complications after surgery is the application of new techniques, a new approach is pertinent in the design of medical implants to reduce bacterial infections. We have designed and tested antibiotic-containing biocomposite thin films of polylactic acid (PLA), and coralline-derived hydroxyapatite (HAp) as controlled drug delivery systems for the treatment of dental, orthopaedic and neural implant-related post-operative infections. These films can be applied to complicated designs of dental, miniaturized neural devices, cochlear or total hip replacement (THR) implants by spray or dip-coating techniques. Current results reveal that the devices could release antibiotic in a controlled manner to prevent significantly bacterial growth and biofilm production. Hydroxyapatite within the composites controls the release rate and also supplies minerals, such as calcium Ca2+ and phosphate PO42− ions, which are essential minerals for bone tissue regeneration. It is concluded from the physical, mechanical and biological properties that these coatings and devices could easily be utilized in a wide range of biomedical applications.
Hydroxyapatite/PLA Biocomposite thin Films for Slow Drug Delivery of Antibiotics for the Treatment of Bone And Implant-Related Infections
(2016-03) Macha, Innocent J; Ben-Nissan, Besim; Santos, Jerran; Cazalbou, Sophie; Milthorpe, Bruce K.
rug delivery systems were developed from coralline hydroxyapatite (HAp) and biodegradable polylactic acid (PLA). Gentamicin (GM) was loaded in either directly to PLA (PLAGM) or in HAp microspheres. Drug loaded HAp was used to make thin film composites (PLAHApGM). Dissolution studies were carried out in phosphate buffered saline (PBS. The release profiles suggested that HAp particles improved drug stabilization and availability as well control the release rate. The release also displays a steady state release. In vitro studies in human Adipose Derived Stem Cells (hADSCs) showed substantial quantities of cells adhering to hydroxyapatite containing composites. The results suggested that the systems could be tailored to release different clinical active substances for a wide range of biomedical applications.
Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery
(2015-01) Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate; Milthorpe, Bruce K.
Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.
Multifunctional-Dual Drug Delivery Poly-Lactic Acid Biocomposite Coating with Hydroxyapatite for Bone Implants
(Trans Tech Publications Inc, 2018-10) Karacan, Ipek; Chou, Joshua; Macha, Innocent J; Cazalbou, Sophie; Milthorpe, Bruce
The new novel implant designs include the functionality of advanced drug delivery systems in order to improve osteointegration and to inhibit the implant-related post-operative infections. In this research, Ti6Al4V metallic implants were coated with the multifunctional-dual slow drug delivery coating which includes a polymeric matrix system based on a poly-lactic acid thin film and a bioactive ceramic hydroxyapatite. This system consists of two different kinds of pharmaceuticals, which are gentamicin and simvastatin. It is reported in this paper that the simvastatin and gentamicin containing poly-lactic acid coating which was applied uniformly and successfully with and without hydroxyapatite microspheres. Most importantly, the release rate of drugs was controlled with PLA matrix and HAp microspheres which have different dissolution rates in order to prevent the high dosages causing adverse side-effects of drugs.
Nanostructured Calcium Phosphates for Drug, Gene, DNA and Protein Delivery and as Anticancer Chemotherapeutic Devices
(2017-06-08) Choi, Andy H.; Macha, Innocent J; Akyol, Sibel; Cazalbou, Sophie; Ben-Nissan, Besim
During the past two decades, a number of materials and devices have been utilised in drug delivery applications. A range of biomaterials with different morphologies and pore sizes are currently utilised. For any given biomaterial or bioceramic, having an adequate control of the chemical composition as well as the critical pore sizes is important in terms of controlling the effectiveness when used to deliver drugs locally. In comparison to all currently known and used biomaterials, given the fact that it possesses chemical similarity to human bone, and most importantly its dissolution characteristics which allow for bone regeneration and growth, calcium phosphate holds a special consideration. Moreover, due to their interconnected pore structure, marine materials such as shells and coral exoskeletons show potential for applications in drug delivery due to their easy conversion to calcium phosphates with controllable dissolution rates. This chapter covers a range of current methods used specifically for natural materials that can be converted to calcium phosphates and mixed with polymeric materials as thin film or nanostructured drug, genes, protein and range of delivery and as anticancer chemotherapeutic devices.
Sol-Gel Nanocoatings of Bioceramics
(Springer, 2014-12) Ben-Nissan, Besim; Choi, Andy H.; Macha, Innocent J; Cazalbou, Sophie
The ability to produce homogeneous high-purity materials is of great interest to industrial and medical applications. In addition, the chemical and physical changes observed at the nanoscale and their influence on properties have been an important academic interest. The gel-structure transition plays a critical role in the formation as well as the current production of various types of sol-gel-derived materials such as nanopowders, nanofibers, nanocoatings, nanocomposites, and solid monoliths. It is the area of thin film coatings produced by sol-gel technology that this chapter covers. In particular, this chapter focuses on the basic synthesis and application methods to produce nanocoatings for biomedical applications. This chapter also attempts to answer some of the pertinent questions related to sol-gel processing and production methods and issues related to the fundamental understanding of the sol-gel process.

Browsing by Author "Cazalbou, Sophie"

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