Carriers Of Therapeutic Agents Research Articles

Room-temperature preparation of phosphate glass microspheres as carriers for therapeutic agents

Event Abstract Back to Event Room-temperature preparation of phosphate glass microspheres as carriers for therapeutic agents Arash Momeni1, Iain Gibson1 and Mark Filiaggi1, 2 1 Dalhousie University, Applied Oral Sciences, Canada 2 Dalhousie University, School of Biomedical Engineering, Canada Introduction: Polymeric microspheres are widely accepted as carriers for therapeutic agents (TA) due to their excellent biocompatibility and biodegradability, however they lack osteoconductivity and mechanical stiffness which glass microspheres (GMS) could offer in dental or bone-related applications. GMS are only prepared by high temperature methods (e.g. propane torch) that preclude loading of TA. Glass particles can be prepared by sol-gel methods and can be loaded by direct addition of the TA to the sol or by subsequent soaking of particles in the TA solution. However, these particles are typically irregular in shape, brittle due to porosity and display low TA encapsulation efficiency. We are describing here for the first time the feasibility of preparing spherical phosphate glass particles with excellent TA loading using polyphosphate coacervates. Materials and Methods: Sodium polyphosphate (NaPP) was prepared in-house [1] and dissolved in water (1% (g/mL)). 1M CaCl2 solution was then added to reach a Ca/P mole ratio of 0.5 forming polyphosphate coacervate [2], which was subsequently collected, freeze-dried and mixed with minocycline (antibiotic) solution (1.6±0.2% minocycline/dry coacervate (wt.)). To form the GMS, 9g of polycaprolactone (thickening agent) was dissolved in 150mL chloroform, followed by addition of 1mL of Span80 (emulsifier). To this solution, 1mL of drug-loaded coacervate was added and mixed using an overhead stirrer at 2000rpm for 90min prior to adding 300mL of acetone and mixing at 400rpm for 3hr. GMS were collected by centrifugation and washed with fresh chloroform and acetone. Cross-sectional SEM imaging of GMS was obtained after imbedding in cured resin, polishing and then applying a conductive coating. Drug loading and encapsulation efficiency were determined by measuring minocycline absorbance at 400nm. Composition was determined by energy dispersive X-ray (EDX) and inductively coupled plasma (ICP). Particle size was assessed using laser diffraction. Results and Discussion: GMS preparation is described schematically in Fig. 1. Ca2+ screens the charge on NaPP chains to yield a coacervate, a polymer-rich phase that separates form the original solution [2]. TA is mixed with the coacervate and then dispersed inside a non-solvent (Chloroform) to obtain spherical particles by surface tension, followed by water extraction (acetone addition) to transform the coacervate to glass. GMS obtained by this process were found to be highly spherical, with homogeneous composition as demonstrated by EDX mapping (Fig. 2). EDX results are in agreement with ICP data indicating a GMS Ca/P mole ratio of 0.4, similar to that observed in the precursor coacervate. A distribution of GMS sizes, between 1-200µm, was obtained that could subsequently be sieved to get to a desired bead size. Encapsulation efficiency was 62±16% (n=6) that is expectedly high as minocycline solubility in acetone and chloroform is limited, and drug loading was 1.0±0.2% (n=6). Higher drug loading is presumably feasible by introducing more minocycline to coacervate initially. Conclusion: Room-temperature preparation of therapeutically loaded phosphate glass microspheres is possible using polyphosphate coacervate precursors. Currently we are focused on minocycline elution studies and application of these microspheres in periodontitis treatment.

Human Serum Albumin as Carrier in Drug Delivery Systems

Recently, human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents against diabetes, cancer, and infectious diseases. Market-approved products include fatty acid derivatives of human insulin for diabetes and the paclitaxel-HSA nanoparticle for various cancers such as metastatic breast cancer and advanced pancreatic cancer. In this review, we focus on the next-generation approach including HSA-binding bioactive gas such as nitric oxide (NO) for treating ischemic/reperfusion injury, cancer, and bacterial infection. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated HSA (SNO-HSA), which is why we are investigating whether this albumin form can be therapeutically useful. Recently, we have developed SNO-HSA analogues such as SNO-HSA with many conjugated SNO groups (poly-SNO-HSA) prepared using chemical modification. Unexpectedly, we found striking inverse effects between poly-SNO-HSA and SNO-HSA. Despite the fact that SNO-HSA inhibits apoptosis, poly-SNO-HSA possesses very strong pro-apoptotic effects against tumor cells. Furthermore, poly-SNO-HSA can reduce or even completely eliminate the multidrug resistance often developed by cancer cells. In this review, we put forward the possibility that poly-SNO-HSA can be used as a safe, effective multifunctional antitumor agent.

Improved Therapeutic Efficacy in Bone and Joint Disorders by Targeted Drug Delivery to Bone.

Site-specific drug delivery to bone is considered achievable using acidic amino acid (L-Asp or L-Glu) homopeptides known as acidic oligopeptides. We found that fluorescence-labeled acidic oligopeptides containing six or more residues bound strongly to hydroxyapatite, which is a major component of bone, and were selectively delivered to and retained in bone after systemic administration. We explored the applicability of this result for drug delivery by conjugation of estradiol and levofloxacin with an L-Asp hexapeptide. We also similarly tagged enzymes (tissue-nonspecific alkaline phosphatase, β-glucuronidase, and N-acetylgalactosamine-6-sulfate sulfatase) and decoy receptors (endogenous secretory receptor for advanced glycation end products and etanercept) to assess whether these would improve therapeutic efficacy. The L-Asp hexapeptide-tagged drugs, including enzymes and decoy receptors, were efficiently delivered to bone in comparison with the untagged drugs. An in vivo experiment confirmed the efficacy of L-Asp hexapeptide-tagged drugs on bone and joint disorders, although there was some loss of bioactivity of estradiol and levofloxacin in vitro, suggesting that the acidic hexapeptide was partly removed by hydrolysis in the body after delivery to bone. It was expected that the ester linkage to the hexapeptide would be susceptible to hydrolysis in situ, releasing the drug from the acidic oligopeptide. These results support the usefulness of acidic oligopeptides as bone-targeting carriers for therapeutic agents. We present some pharmacokinetic and pharmacological properties of the L-Asp hexapeptide-tagged drugs.

Development of orally available bile acid conjugated nanoparticle using heparin and protamine

Event Abstract Back to Event Development of orally available bile acid conjugated nanoparticle using heparin and protamine Jooho Park1 and Youngro Byun1, 2 1 Seoul National University, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Korea 2 Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Scie, Korea Oral delivery is the most clinically acceptable delivery route for patients. However, it is hard to deliver some therapeutic agents including macromolecule, peptide and gene. For decades, several researchers have tried to develop an oral agent for macromolecule delivery [1],[2]. Especially, nanoparticles and nanocomplex are remarkable carriers for therapeutic agents, but, they are not usually available as an oral tablet [3]. Here, we developed a new nanoparticle using two FDA-approved biomaterials for oral delivery. A negatively charged heparin and positively charged peptide named protamine have shown clinical therapeutic potential [4]. Using the polysaccharide, peptide and bile acids, we have designed an orally available nanoparticle. It was possible to control the surface charge and the size of nanoparticle by using the formulation of heparin and protamine. Moreover, the bile acids in nanoparticle enhanced the oral delivery of the nanoparticle. This nanoparticle could bind to the apical sodium-dependent bile acid transporter (ASBT) on caco-2 and MDCK cell. In addition, the nanoparticles were not in the tight junctions but they were present in the transcellular region; chitosan-based positive nanoparticles are usually absorbed via paracellular route. Furthermore, cy5-conjugated nanoparticle was treated to rats and mice to detect the nanoparticles in the GI tract. The orally treated nanoparticles were absorbed in the ileum, and then the retention period of the nanoparticles was also measured by using cy5 signals. In conclusion, these results represent an advanced major oral delivery technique for drug and gene delivery. The oral delivery of safe and functional nanoparticles would invoke the benefits of advanced oral delivery system providing a clinical therapeutic potential. This study was supported by grants from the Bio & Medical Technology Development Program (grant no. 2012028833). The authors thank National Center for Inter-University Research Facilities for technical assistance.

Polymeric pharmaceutical forms - the forms of the future

800x600 Polymers are gaining even more ground as carriers of therapeutic agents because of the potential to modify the properties of clinically proven medicines, which have limited use due to their shortcomings and side effects. Polymeric pharmaceutical systems are able to solve problems such as dose limitation of drug, poor water-solubility and duration of drug action. Polymer-pharmaceutical conjugates enable the improvement of drug localization in target tissue and also to optimize the drug release speed. Of great interest is the development of even cleverer and newer pharmaceutical forms made of polymers of varied reactivity, which allows for their binding with different biologically active substances. Normal 0 21 false false false BG X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Calibri,sans-serif;}

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

Neural stem cell-mediated delivery of oncolytic adenovirus.

The use of stem cells (SCs) as carriers for therapeutic agents has now progressed to early clinical trials. These clinical trials exploring SC-mediated delivery of oncolytic adenoviruses will commence in the near future, hopefully yielding meritorious results that can provoke further scientific inquiry. Preclinical animal studies have demonstrated that SCs can be successfully loaded with conditionally-replicative adenoviruses and delivered to the tumor, whereupon they may evoke pronounced therapeutic efficacy. In this protocol, we describe the maintenance of SCs, provide an analysis of optimal adenoviral titers for SC loading, and evaluate the optimized viral loading on SCs.

Intranasal and intravenous administration of octa-arginine modified poly(lactic-co-glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide.

The potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated. PLGA NPs containing coumarin-6 or loperamide were surface modified using R8 and characterised for size, zeta potential, drug loading and release. We examined the cellular uptake of NPs in Madin-Darby Canine Kidney (MDCK) cells and CNS delivery of loperamide in a mouse model following intranasal (i.n.) and intravenous (i.v.) administration. NPs were 300-350 nm in diameter and of negative zeta potential which neutralised on R8 conjugation. Cellular uptake of R8-PLGA NPs was rapid compared with PLGA NPs and correlated with a high antinociceptive effect in mice by both the i.n. and i.v. routes. Little antinociceptive effect for PLGA NPs was observed reflecting their slow uptake in the in-vitro cell model. This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.

Core-shell-type magnetic mesoporous silica nanocomposites for bioimaging and therapeutic agent delivery.

Advances in nanotechnology and nanomedicine offer great opportunities for the development of nanoscaled theranostic platforms. Among various multifunctional nanocarriers, magnetic mesoporous silica nanocomposites (M-MSNs) attract prominent research interest for their outstanding properties and potential biomedical applications. This Research News article highlights recent progress in the design of core-shell-type M-MSNs for both diagnostic and therapeutic applications. First, an overview of synthetic strategies for three representative core-shell-type M-MSNs with different morphologies and structures is presented. Then, the diagnostic functions of M-MSNs is illustrated for magnetic resonance imaging (MRI) applications. Next, magnetic targeted delivery and stimuli-responsive release of drugs, and effective package of DNA/siRNA inside mesopores using M-MSNs as therapeutic agent carriers are discussed. The article concludes with some important challenges that need to be overcome for further practical applications of M-MSNs in nanomedicine.

Recent advances in the development of functionalized carbon nanotubes: a versatile vector for drug delivery

Carbon nanotubes (CNTs) possess unique physical and chemical properties and can serve as a platform for transporting a variety of bioactive molecules, such as drugs, proteins, and genes, given appropriate surface modifications. Here, we present an overview of the progress in applying CNTs as therapeutic agent carriers. Drugs can be attached to CNTs either through supramolecular chemistry to form noncovalent assembly or via covalent linkage to the functional groups preinstalled on CNTs. In addition to surface loading, packing of molecules inside the internal cavity of CNTs to protect less stable entities has also been achieved. Besides drugs, the high specific surface area of CNTs can also allow the installation of multiple molecules with different functions, e.g. target recognition and optical imaging, simultaneously to achieve synergistic effects. The drug release process tends to be gradual and sustained after being attached to CNTs, and could be tuned by various factors, such as pH, diameter of CNTs, and target recognition. The content throughout this review is mainly focused on the different protocols of loading drugs onto or into CNTs as well as how to control the drug release.

Glucose-Coated Gold Nanoparticles Transfer across Human Brain Endothelium and Enter Astrocytes In Vitro

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

Trajectory Simulation of Magnetic Nanoparticles in the Blood Vessel for the Magnetic Targeted-Drug Delivery

Magnetic nanoparticles (MNPs) have been considered as potential therapeutic agent carrier for the magnetic targeted-drug delivery in the fight against cancer. Trajectories of MNPs in the blood vessel determine the capture and retention ratio, and the final effectiveness of the treatment. In the present study, a theoretical model of MNPs trajectory is deduced at first. Then two kinds of magnets are proposed, and their magnetic field distributions are calculated through the finite element method software of ANSYS. Using the model and magnetic field inputs, the MNPs trajectories are determined, and the influences of the MNP diameter (Rp), the blood flow velocity (vf) and magnetic field intensity (H) on the trajectories are clarified finally. It is found that the proposed method combining the theoretical model and numerical simulation is feasible. The closed magnetic circuit with concave-convex poles has better MNPs retention ratio than that of the open magnetic circuit because it has higher H and Grad (H). LargeRp, lowvf, and high H are good to capture the MNPs. Especiallyvfand H are critical parameters for the retention ratio of MNPs, and highvfand low H may let MNPs escape the magnetic field region.

Nanotherapeutics and Nano-Imaging in Biotransport

Nanotherapeutics and Nano-Imaging in Biotransport

Stimulus-Responsive Controlled Release System by Covalent Immobilization of an Enzyme into Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug delivery carriers for therapeutic agents. Herein, we explored the covalent immobilization of proteins into MSN to generate a stimulus-responsive controlled release system. First, MSN were functionalized with thiol groups using (mercaptopropyl)-trimethoxysilane (MPTMS). Functionalization was verified by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering. The model enzyme carbonic anhydrase (CA) was coupled to sulfosuccinimidyl 6-[3'(2-pyridyldithio)-propionamido]hexanoate (Sulfo-LC-SPDP) at a low ratio of 1:1 to prevent enzyme inactivation and subsequently covalently immobilized into MSN via thiol-disulfide interchange. The enzyme could be released from MSN with 10 mM glutathione, which represents intracellular redox conditions, while it remained bound to the MSN at extracellular redox conditions represented by 1 μM glutathione. The activity of the released enzyme was >80% demonstrating that the enzyme was still largely functional and active after immobilization and release. Human cervical cancer (HeLa) cells were incubated with the MSN-CA bioconjugates at various concentrations for 24 h and the data show good biocompatibility. In summary, we demonstrate the potential of MSN as drug delivery systems for proteins.

Well-defined hydroxyapatite–polycation nanohybrids via surface-initiated atom transfer radical polymerization for biomedical applications

The ability to manipulate and control the surface properties of hydroxyapatite (HA) nanoparticles is of crucial importance for the design of HA-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of (2-dimethyl amino)ethyl methacrylate (DMAEMA) is first employed to tailor the functionality of HA surfaces in a well-controlled manner and to produce a series of new cationic hybrids (termed as HA-PDM). The HA parts of HA-PDM were coated by different lengths of PDMAEMA chains. The HA-PDM exhibited a good ability to condense plasmid DNA (pDNA) with suitable particle size and a zeta potential for gene transfection. Most importantly, in comparison with PDMAEMA homopolymers, the HA-PDM displayed considerably enhanced buffering capacity, and exhibited much higher gene transfection efficiencies in different cell lines, including osteoblast MC3T3 and osteosarcoma MG63 cells. In addition, the HA-PDM/pDNA complexes also could largely enhance the differentiation of preosteoblast cells. Such well-defined HA-PDM nanohybrids possess great potential applications as new drug-delivery vectors in bone tissue engineering.

Preparation and evaluation of well-defined hemocompatible layered double hydroxide-poly(sulfobetaine) nanohybrids

The ability to manipulate and control the surface properties of layered double hydroxide (LDH) nanoparticles is of crucial importance in the designing of LDH-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of zwitterionic 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) is first employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined hemocompatible hybrids (termed as LDHPS). The blood compatibilities of the modified LDH nanoparticles were investigated using coagulation tests, complement activation, platelet activation, hemolysis assay, morphological changes of red blood cells, and cytotoxicity assay. The results confirmed that the P(DMAPS) grafting can substantially enhance the hemocompatibility of the LDH particles, and the LDHPS hybrids can be used as biomaterials without causing any hemolysis. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer chains, the LDH nanoparticles with desirable blood properties can be readily tailored to cater to various biomedical applications.

Interferon-β efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis

Neovascularization has a critical role in the growth and metastatic spread of tumors, and involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow. In this study, we examined whether EPCs could promote tumor angiogenesis, and found that the tumor growth was enhanced by the administration of EPCs. To test the hypothesis that genetically modified bone marrow-derived EPCs can be effective carriers of therapeutic agents to tumor sites, we conducted human interferon-beta (HuIFN-β) gene transfection of EPCs with a virus vector in vitro. When HuIFN-β was applied in the ex vivo culture of EPCs, HuIFN-β-transduced EPCs achieved efficient killing of the total population of SPC-A1 cells, indicating a bystander effect was elicited by HuIFN-β-transduced EPCs in vitro. When SCP-A1 cancer cells were coimplanted along with ex vivo cultivated EPCs subcutaneous injection in nude mice, the tumor growth was increased. However, the anti-tumor effect of interferon-beta (IFN-β) offset the tumor-progressive character of EPCs and the tumor growth, and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon IFN-β treatment. In addition, overall expression levels of vascular endothelial growth factor in tumor tissues were decreased upon IFN-β treatment. Therefore, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system.

Physical characterization and cellular uptake of propylene glycol liposomes in vitro

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes–propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index = 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.

Herbal drug incorporated antibacterial nanofibrous mat fabricated by electrospinning: An excellent matrix for wound dressings

AbstractNano‐components and nano‐systems for health care and medical applications are the focus of many research projects worldwide. Nanofibrous membranes are highly soft materials with high surface‐to‐volume ratios, and therefore can serve as excellent carriers for therapeutic agents that are antibacterial or accelerate wound healing. PCL/PVP Nanofiber mat containing chloroform: methanol (4:1) crude bark extract of Tecomella undulata, a medicinal plant widely known for its traditional medical applications including its wound healing ability, were prepared and evaluated for their antibacterial properties. With good drug stability and high drug‐loading efficacy, the incorporation of herbal extract in the polymer media did not appear to influence the morphology of the resulting fibers, as both the drug‐free and the drug‐loaded nanofibers remained unaltered, microscopically. Activity was tested against standard strains of Pseudomonas aeruginosa MTCC 2297, Staphylococcus aureus ATCC 933, Escherichia coli (IP‐406006). Extract loaded PCL/PVP nanofiber mat were able to inhibit the growth of the bacterial strains which indicate that it could act not only as a drug delivery system but also in the treatment of wound healing or dermal bacterial infections thereby proving a potential application for use as a wound dressing. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Investigation of the interaction of biodegradable micro- and nanoparticulate drug delivery systems with platelets

Biodegradable micro- and nanoparticles are being increasingly investigated for drug delivery and targeting of therapeutics. The size and surface properties of these particles are important factors influencing their interaction and uptake by various cells, tissues and organs. Optimising these properties, to enhance cellular uptake, may increase their potential for interaction with other physiological components such as platelets resulting in platelet activation and inappropriate thrombus formation. The aim of this study was to investigate the potential interaction of particulates with platelets. Biodegradable micro- and nanoparticles based on poly-lactide-co-glycolide (PLGA), poly-lactide-co-glycolide-macrogol (PLGA-macrogol) and chitosan were prepared using solvent evaporation, spray drying or solvent dispersion techniques. Microparticles formulated had a median diameter (D50%) of 2-9 µm, while nanoparticles had an average diameter of 100-500 nm. The surface morphology ranged from smooth and spherical to irregular depending on polymer and preparation method used. Particles, reconstituted in the concentration range of 0.1-500 µg/ml, were tested for their ability to induce or inhibit platelet aggregation. No effects on either induction of platelet activity or inhibition of aggregation were detected. None of the particles examined were found to alter platelet activity. These results suggested that the biodegradable micro- and nanoparticles tested were safe for use as potential drug carriers of therapeutic agents.