Spomenka Simovic

University of South Australia , Tarndarnya, South Australia, Australia

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Publications (40)144.25 Total impact

  • Roya Yadollahi, Krasimir Vasilev, Spomenka Simovic
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    ABSTRACT: Poor aqueous solubility of some drug molecules is a major problem in drug formulation. Drug nanosuspensions emerged as one solution to delivering such hydrophobic drugs. Scaling down to nanoparticles enhances drug aqueous solubility and bioavailability by increasing drug surface area that comes into contact with biological media. Nanosuspensions that have attracted particular attention are those sterically stabilised by steric polymers such as polyethylene glycol (PEG) with a typical size range of 10–100 nm. These nanoparticles are capable of accumulating in targeted areas such as cancer tissues and infarct zones with minimal damage to healthy tissues. Nanosuspensions are often prepared by commercially available methods such as high pressure homogenization, media milling, emulsification, and melt emulsification. Solidification and surface modification methods are post-processing techniques used to add particular properties for advanced therapies. In this review, we firstly describe preparation methods for nanosuspensions. Secondly, we highlight typical characterization techniques. Finally, we describe several practical application of applications for drug delivery design and different administration routes such as parenteral, pulmonary, oral, and ocular.
    Journal of Nanomaterials 10/2014; · 1.55 Impact Factor
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    ABSTRACT: We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self - emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/ lecithin/ propylene glycol/ caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3 - dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self - emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40°C and 70% RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ - loaded SEPS can maintain initial CBZ characteristics.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2014; · 2.61 Impact Factor
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    ABSTRACT: a b s t r a c t We report on a platform for extended release of biologically-active therapeutic antibodies. Extended antibody release has been achieved by utilising a plasma polymer film of controlled and predetermined thickness deposited on the top of a porous platform loaded with rituximab. Antibody release kinetics directly correlates to the plasma polymer film thickness that is in turn controlled by the plasma polymer deposition time. After 1 month, 82%, 60% and 45% of the antibody is released from platforms coated with plasma polymer for 50 s, 150 s and 300 s, respectively. Activity of the released antibody was assessed in cultures of CD20-positive Daudi cells by using polyacrylamide gel electrophoresis and flow cytometry. The results from gel electrophoresis and flow cytometry indicate that the antibody had maintained its integrity during the release process. This work provides a proof-of-concept technology that achieves extended release of biologically active rituximab for more than 30 days. & 2014 Elsevier B.V. All rights reserved.
    01/2014;
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    ABSTRACT: The aim of the present research is to formulate and evaluate polymeric nanosuspensions containing three model water insoluble drugs, nifedipine (NIF), carbamazepine (CBZ), and ibuprofen (IBU) with various physicochemical properties. The nanosuspensions were prepared from hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) by a cosolvent technique with polyethylene glycol (PEG-300) and water as the cosolvents. Physicochemical and morphological characteristics of the nanosuspensions (particle size, polydispersity index, and crystallinity) have been correlated with the drug release behaviour. The effects of polymer, drug ratio on the physical, morphological, and dissolution characteristics of the drugs are reported. Drug release is significantly enhanced from the nanosuspensions; for example, the maximum NIF, IBU, and CBZ concentrations after 8-hour dissolution are increased approximately 37, 2, and 1.2 times, respectively, in comparison with the pure powdered drugs. Based on this solubilization enhancement performance, the nanosuspensions have potential for increasing the orally dosed bioavailability of NIF, IBU, and CBZ.
    Journal of Nanomaterials 10/2013; 2013. · 1.55 Impact Factor
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    ABSTRACT: The structure and stability of emulsions formed in the presence of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) were characterised. From oil-water contact angles on PLGA films, it was deduced that particle surface hydrophobicity is linked to the oil phase polarity. Incorporation of polyvinyl alcohol molecules into the nanoparticle surfaces reduces the particle hydrophobicity sufficiently for oil-in-water emulsions to be preferentially stabilised. PLGA nanoparticles enhance the stability of emulsions formed from a wide range of oils of different polarities. The nanoparticle concentration was found to be a key parameter controlling the average size and coalescence stability of the emulsion drops. Visualisation of the interfacial structure by electron microscopy indicated that PLGA nanoparticles were located at the drop surfaces, evidence of the capacity of these particles to stabilise Pickering-type emulsions. These results provide insights into the mechanism of PLGA nanoparticle stabilisation of emulsions.
    Journal of Colloid and Interface Science 03/2012; 375(1):142-7. · 3.55 Impact Factor
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    ABSTRACT: The use of porous silica microshells (microparticles) generated from fossilised diatoms known as diatomite or diatomaceous earth (DE) as a natural drug carrier for drug delivery application is presented. The structure, morphology, particle size distribution, porosity, surface area and crystallinity of diatom microshells obtained from Australian mine (Mount Sylvia Diatomite Pty. Ltd.) were characterised using scanning electron microscopy, particle size measurements, BET analysis and X-ray powder diffraction analysis. To prove the drug delivery concept based on diatoms for implant and oral drug delivery, indomethacin as a model of water poorly soluble drug was investigated. Results show the effectiveness of diatom silica for drug delivery application, with about 22wt.% drug loading capacity and sustained drug release over two weeks. Two steps drug release from diatom structures were observed: the first is rapid release (over 6h) attributed to the surface deposited drug and the second is slow and sustained release over two weeks with zero order kinetics, as a result of release from diatom pores and internal hollow structure. These results confirm that natural material based on diatom silica can be successfully applied as a biocarrier for both oral and implant drug delivery applications, offering considerable potential to replace synthetic silica based materials.
    Powder Technology - POWDER TECHNOL. 01/2012;
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    ABSTRACT: Submicron oil-in-water (o/w) emulsions stabilised with conventional surfactants and silica nanoparticles were prepared and freeze-dried to obtain free-flowing powders with good redispersibility and a three-dimensional porous matrix structure. Solid-state emulsions were characterised for visual appearance, particle size distribution, zeta potential and reconstitution properties after freeze-drying with various sugars and at a range of sugar to oil ratios. Comparative degradation kinetics of all-trans-retinol from freeze-dried and liquid emulsions was investigated as a function of storage temperatures. Optimum stability was observed for silica-coated oleylamine emulsions at 4 °C in their wet state. The half-life of all-trans-retinol was 25.66 and 22.08 weeks for silica incorporation from the oil and water phases respectively. This was ∼4 times higher compared to the equivalent solid-state emulsions with drug half-life of 6.18 and 6.06 weeks at 4 °C. Exceptionally, at a storage temperature of 40 °C, the chemical stability of the drug was 3 times higher in the solid-state compared to the wet emulsions which confirmed that freeze-drying is a promising approach to improve the chemical stability of water-labile compounds provided that the storage conditions are optimised.
    International Journal of Pharmaceutics 12/2011; 423(2):384-91. · 3.99 Impact Factor
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    ABSTRACT: Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.
    Nanoscale 12/2011; 4(4):1220-30. · 6.73 Impact Factor
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    ABSTRACT: Nanoscience and Nanotechnology (ICONN), 2010 International Conference on A two-step electrochemical anodisation approach was adopted in this work to create a series of highly ordered mesopores etched with different diameter (60 to 160 nm) and uniform nanotube length in anodised aluminium oxide (AAO). The loading and release characteristics of model drug (indomethacin) and drug carriers (micelles named Pluronic F127, TPGS, PEO-PPO-PEO) were presented to investigate the influence of micelle size, pore diameter and surface modification of AAO on release studies. Surface chemistry was varied via silanation process, using AFTES and PFPTES. It was discovered that quicker release of drugs was induced by larger pore size and smaller micelles. Moreover drug release was found to favour hydrophobic surface as the release was faster in PFPTES modified AAO than the one with APTES.
    Proceedings of the IEEE 10/2011; · 6.91 Impact Factor
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    ABSTRACT: This study explores the use of natural silica-based porous material from diatoms, known as diatomaceous earth, as a drug carrier of therapeutics for implant- and oral-delivery applications. To prove this concept, two drugs models were used and investigated: a hydrophobic (indomethacin) and hydrophilic (gentamicin). Results show the effectiveness of diatom microcapsules for drug-delivery application, showing 14-22 wt% drug loading capacity and sustained drug release over 2 weeks. Two steps in the drug release from diatom structures were observed: the first, rapid release (over 6 h is attributed to the surface deposited drug) and the second, slow and sustained release over 2 weeks with zero order kinetics. These results confirm that natural material based on diatom silica can be successfully applied as a drug carrier for both oral and implant drug-delivery applications, offering considerable potential to replace existing synthetic nanomaterials.
    Nanomedicine 06/2011; 6(7):1159-73. · 5.26 Impact Factor
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    ABSTRACT: Nanopore and nanotube structures such as anodic aluminium oxide (AAO) and nanotubular titania (TNT) prepared by self-ordering electrochemical anodization have attracted considerable attention for the development of new implant devices and drug delivery applications. In this work, we present a new implantable drug delivery system that integrates polymer micelles as drug nanocarrier and nanoporous structure to achieve an extended delivery of poorly water soluble drugs. Two strategies for controlled release of nanocarriers from AAO and TNT platforms were explored: (i) the influence of pore diameters of AAO (65 nm to 160 nm) and nanocarrier diameters (15–75 nm) and (ii) application of thin film-plasma polymer layer on the surface of porous material. By varying pore and polymer micelles diameters a two-phase release kinetics with burst release of 31–55% in the first 6–8 h followed by the slow phase, spanning across 8–22 days were obtained. Nevertheless, although results were improved by varying pore diameters, it is still not the optimal strategy to achieve a slow release of drug nanocarriers from porous platforms. More effective method to achieve their extended release with zero-order kinetics was demonstrated using plasma polymerisation method, in which complete release of micelles was found to be delayed to 27–31 days, with a significantly lowered burst release (12–15%).
    Journal of Materials Chemistry 05/2011; 21(20):7082-7089. · 6.63 Impact Factor
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    ABSTRACT: In this paper, we present recent work from our group focussed on the fabrication of nanopore and nanotube arrays using self-ordered electrochemistry, and their application in several key areas including template synthesis, molecular separation, optical sensing, and drug delivery. We have fabricated nanoporous anodic aluminium oxide (AAO) with controlled pore dimensions (20–200 nm) and shapes, and used them as templates for the preparation of gold nanorod/nanotube arrays and gold nanotube membranes with characteristic properties such as surface enhanced Raman scattering and selective molecular transport. The application of AAO nanopores as a sensing platform for reflective interferometric detection is demonstrated. Finally, a drug release study on fabricated titania nanotubes confirms their potential for implantable drug delivery applications.
    Australian Journal of Chemistry 04/2011; 64:294-301. · 1.87 Impact Factor
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    ABSTRACT: The interfacial and bulk properties of submicron oil-in-water emulsions simultaneously stabilised with a conventional surfactant (either lecithin or oleylamine) and hydrophilic silica nanoparticles (Aerosil®380) were investigated and compared with emulsions stabilised by either stabiliser. Emulsions solely stabilised with lecithin or oleylamine showed poor physical stability, i.e., sedimentation and the release of pure oil was observed within 3 months storage. The formation and long-term stability of silica nanoparticle-coated emulsions was investigated as a function of the surfactant type, charge, and concentration; the oil phase polarity (Miglyol®812 versus liquid paraffin); and loading phase of nanoparticles, either oil or water. Highly stable emulsions with long-term resistance to coalescence and creaming were formulated even at low lecithin concentrations in the presence of optimum levels of silica nanoparticles. The attachment energy of silica nanoparticles at the non-polar oil-water interface in the presence of lecithin was significantly higher compared to oleylamine in line with good long-term stability of the former compared to the sedimentation and release of oil in the latter. The attachment energy of silica nanoparticles at the polar oil-water interface especially in the presence of oleylamine was up to five-times higher compared to the non-polar liquid paraffin. The interfacial layer structure of nanoparticles (close-packed layer of particle aggregates or scattered particle flocs) directly related to the free energy of nanoparticle adsorption at both MCT oil and liquid paraffin-water interfaces.
    Journal of Colloid and Interface Science 03/2011; 358(1):217-25. · 3.55 Impact Factor
  • Li Hui Lim, Angel Tan, Spomenka Simovic, Clive A Prestidge
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    ABSTRACT: This study reports on the physicochemical characterisation and in vitro investigations of macro-porous silica-lipid hybrid (SLH) microcapsules when formulated using various lipids: long-chain triglycerides (LCT), medium-chain triglycerides (MCT), medium-chain mono-, diglycerides (MCMDG); and emulsifiers: anionic lecithin and cationic oleylamine. For the lipophilic compound coumarin 102 (logP=4.09), a complete and immediate in vitro release was attained for the SLH microcapsules under simulated intestinal sink conditions. The in vitro digestion study of various types of SLH microcapsules demonstrates: (i) reduced variability and enhanced lipid digestibility for the MCMDG-based microcapsules (i.e. 90-100% lipolysis) in comparison with an equivalent lipid solution and emulsion (50-90% lipolysis); and (ii) more controllable digestion kinetics for the LCT-based microcapsules which produce a lipolysis rate higher than that of a lipid solution but lower than that of a lipid emulsion. The drug phase partition results show approximately 5- to 17-fold increase in the drug solubilisation degree resulting from the digestion of MCT and MCMDG-based microcapsules (116 μg/mL), and LCT-based microcapsules (416 μg/mL) in comparison with the blank micellar medium (24 μg/mL). In conclusion, the SLH microcapsules could be tailored to manipulate the digestion patterns of both medium- and long-chain lipids in order to maximise the drug solubilisation capacity.
    International Journal of Pharmaceutics 02/2011; 409(1-2):297-306. · 3.99 Impact Factor
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    ABSTRACT: In this review article we collect and analyse preparation, chemistry and properties of silica materials relevant for drug delivery applications. We review some of the most relevant milestones in the research of silica materials for implantable, oral, intravenous and dermal drug delivery systems. Preparation, chemistry and drug delivery characteristics of fumed silica nanoparticles (oral and dermal delivery route), silica xerogels (implant delivery), mesoporous silica materials (implant and oral delivery) and mesoporous silica spheres (intravenous delivery) with particular emphasis on their role in anticancer therapy and the design of stimuli responsive drug delivery systems are analysed. Recent progress in the research of silica materials for controlled drug delivery, namely, biocompatibility aspects, research on hybrid materials, anticancer and stimuli-responsive mesoporous silica materials are particularly emphasized.
    Current Drug Discovery Technologies 02/2011; 8(3):269-76.
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    ABSTRACT: Diatom silica microcapsules prepared by purification of diatomaceous earth (DE) were functionalised by dopamine modified iron-oxide nanoparticles, in order to introduce diatoms with magnetic properties. The application of magnetised diatoms as magnetically guided drug delivery microcarriers has been demonstrated.
    Chemical Communications 09/2010; 46(34):6323-5. · 6.38 Impact Factor
  • Spomenka Simovic, Peter Heard, Clive A Prestidge
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    ABSTRACT: We report on the fabrication of dry hybrid lipid-silica microcapsules for enhanced lipid hydrolysis using Pickering emulsion templates formed by interfacial nanoparticle-emulsifier electrostatic interaction. The microcapsules are produced by controlled precipitation of emulsion droplets by oppositely charged silica nanoparticles at room temperature. Microcapsule formation is driven by the interfacial structure of the initial Pickering emulsion, which is in turn controlled by the nanoparticle to lipid ratio. In the region of charge reversed, precipitated and aggregated droplets, droplet-nanoparticle networks have been identified by freeze-fracture SEM imaging. The microcapsules have diameters in the range 20-50 mum and contain approximately 65% oil distributed within an internal matrix structure composed of a labyrinth of interconnected pores approximately 20-100 nm. Pore distribution and diameters depend on the silica to nanoparticle ratio that in turn determines droplet coating and stability. The microcapsules facilitate enhanced lipid hydrolysis kinetics, i.e. their pseudo first-order rate constant for lipid hydrolysis is approximately 3 times greater than for equivalent submicron lipid droplets. This behaviour is attributed to the increased oil surface area within the microcapsule due to the specific porous structure that causes rapid release of submicron and micron size oil droplets. The simple route for fabrication of porous microcapsule morphologies may present new opportunities for applications in encapsulation, delivery, coatings, and catalysis.
    Physical Chemistry Chemical Physics 07/2010; 12(26):7162-70. · 4.20 Impact Factor
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    ABSTRACT: We report on a porous silica-lipid hybrid microcapsule (SLH) oral delivery system for indomethacin fabricated from Pickering emulsion templates, where the drug forms an electrostatic complex with cationic lipid present in the oil phase. Dry SLH microcapsules prepared either by spray drying (approximately 1-5 microm) or phase coacervation (20-50 microm) exhibit a specific internal porous matrix structure with pore diameters in the range of 20 to 100 nm. Dissolution studies under sink conditions and in the presence of electrolytes revealed a decreased extent of dissolution; this confirms the lipophilic nature the drug-lipid complex and its location in the oil phase. Orally dosed in-vivo studies in rats showed complete drug absorption and statistically higher fasted state bioavailability (F) (p<0.05) in comparison to aqueous suspensions and o/w submicron emulsions of indomethacin. It is postulated that the SLH microcapsules improve oral absorption via complete solubilisation of drug-lipid electrostatic complexes during enzymatic lipolysis in the GI track.
    Journal of Controlled Release 05/2010; 143(3):367-73. · 7.63 Impact Factor
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    ABSTRACT: We investigate the role of hydrophilic fumed silica in controlling the digestion kinetics of lipid emulsions, hence further exploring the mechanisms behind the improved oral absorption of poorly soluble drugs promoted by silica-lipid hybrid (SLH) microcapsules. An in vitro lipolysis model was used to quantify the lipase-mediated digestion kinetics of a series of lipid vehicles formulated with caprylic/capric triglycerides: lipid solution, submicrometer lipid emulsions (in the presence and absence of silica), and SLH microcapsules. The importance of emulsification on lipid digestibility is evidenced by the significantly higher initial digestion rate constants for SLH microcapsules and lipid emulsions (>15-fold) in comparison with that of the lipid solution. Silica particles exerted an inhibitory effect on the digestion of submicrometer lipid emulsions regardless of their initial location, i.e., aqueous or lipid phases. This inhibitory effect, however, was not observed for SLH microcapsules. This highlights the importance of the matrix structure and porosity of the hybrid microcapsule system in enhancing lipid digestibility as compared to submicrometer lipid emulsions stabilized by silica. For each studied formulation, the digestion kinetics is well correlated to the corresponding in vivo plasma concentrations of a model drug, celecoxib, via multiple-point correlations (R(2) > 0.97). This supports the use of the lipid digestion model for predicting the in vivo outcome of an orally dosed lipid formulation. SLH microcapsules offer the potential to enhance the oral absorption of poorly soluble drugs via increased lipid digestibility in conjunction with improved drug dissolution/dispersion.
    Molecular Pharmaceutics 04/2010; 7(2):522-32. · 4.57 Impact Factor
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    Spomenka Simovic, Dusan Losic, Krasimir Vasilev
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    ABSTRACT: In this communication, we present a novel approach for control of drug release from porous materials. The method is based on deposition of a plasma polymer layer with controlled thickness which reduces a pore diameter and, hence, defines the rate of drug release.
    Chemical Communications 02/2010; 46(8):1317-9. · 6.38 Impact Factor