Novel biodegradable fibres for applications in tissue engineering and drug delivery

The preparation and characterisation of novel biodegradable polymer fibres for application in tissue engineering and drug delivery are reported. Poly(e-caprolactone) (PCL) fibres were produced by wet spinning from solutions in acetone under low shear (gravity flow) conditions. The tensile strength and stiffness of as-spun fibres were highly dependent on the concentration of the spinning solution. Use of a 6% w/v solution resulted in fibres having strength and stiffness of 1.8 MPa and 0.01 GPa respectively, whereas these values increased to 9.9 MPa and 0.1 GPa when fibres were produced from 20% w/v solutions. Cold drawing to an extension of 500% resulted in further increases in fibre strength (up to 50 MPa) and stiffness (0.3 GPa). Hot drawing to 500% further increased the fibre strength (up to 81 MPa) and stiffness (0.5 GPa). The surface morphology of as-spun fibres was modified, to yield a directional grooved pattern by drying in contact with a mandrel having a machined topography characterised by a peak-peak separation of 91 mm and a peak height of 30 mm. Differential scanning calorimetery (DSC) analysis of as-spun fibres revealed the characteristic melting point of PCL at around 58°C and a % crystallinity of approximately 60%. The biocompatibility of as-spun fibres was assessed using cell culture. The number of attached 3T3 Swiss mouse fibroblasts, C2C12 mouse myoblasts and human umbilical vein endothelial cells (HUVECs) on as-spun, 500% cold drawn, and gelatin coated PCL fibres were observed. The results showed that the fibres promoted cell proliferation for 9 days in cell culture and was slightly lower than on tissue culture plastic. The morphology of all cell lines was assessed on the various PCL fibres using scanning electron microscopy. The cell function of HUVECs growing on the as-spun PCL fibres was evaluated. The ability HUVECs to induce an immune response when stimulated with lipopolysaccaride (LPS) and thereby to increase the amount of cell surface receptors was assessed by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that PCL fibres did not inhibit this function compared to TCP. As-spun PCL fibres were loaded with 1 % ovine albumin (OVA) powder, 1% OVA nanoparticles and 5% OVA nanoparticles by weight and the protein release was assessed in vitro. PCL fibres loaded with 1 % OVA powder released 70%, 1% OVA nanoparticle released 60% and the 5% OVA nanoparticle released 25% of their protein content over 28 days. These release figures did not alter when the fibres were subjected to lipase enzymatic degradation. The OVA released was examined for structural integrity by SDS-PAGE. This showed that the protein molecular weight was not altered after incorporation into the fibres. The bioactivity of progesterone was assessed following incorporation into PCL fibres. Results showed that the progesterone released had a pronounced effect on MCF-7 breast epithelial cells, inhibiting their proliferation. The PCL fibres display high fibre compliance, a potential for controlling the fibre surface architecture to promote contact guidance effects, favorable proliferation rate of fibroblasts, myoblasts and HUVECs and the ability to release pharmaceuticals. These properties recommended their use for 3-D scaffold production in soft tissue engineering and the fibres could also be exploited for controlled presentation and release of biopharmaceuticals such as growth factors.

Incorporation and release of macromolecules from biodegradable polymer vehicles

The initial objective of this work was to evaluate and introduce fabrication techniques based on W/0/W double emulsion and 0/W single emulsion systems with solvent evaporation for the incorporation of a surrogate macromolecule (BSA) into microspheres and microcapsules fabricated using P(HB-HV}, PEA and their blends. Biodegradation, expressed as changes in the gross and ultrastructural morphology of BSA loaded microparticulates with time was monitored using SEM concomitant with BSA release. Spherical microparticulates were successfully fabricated using both the W/0/W and 0/W emulsion systems. Both microspheres and microcapsules released BSA over a period of 24 to 26 days. BSA release from P(HB-HV)20% PCL 11 microcapsules increased steadily with time, while BSA release from all other microparticulates was characterised by an initial lag phase followed by exponential release lasting 6-11 days. Microcapsules were found to biodegrade more rapidly than microspheres fabricated from the same polymer. The incubation of microparticulates in newborn calf serum; synthetic gastric juice and pancreatin solution showed that microspheres and microcapsules were susceptible to enzymatic biodegradation. The in vitro incubation of microparticulates in Hank's buffer demonstrated limited biodegradation of microspheres and microcapsules by simple chemical hydrolysis. BSA release was thought to ocurr as a result of the macromolecule diffusing through either inherent micropores or via pores and channels generated in situ by previously dissolved BSA. However, in all cases, irrespective of percentage loading or fabrication polymer, low encapsulation efficiencies were obtained with W/0/W and 0/W techniques (4.2±0.9%- 15.5±0.5%,n=3), thus restricting the use of these techniques for the generation of microparticulate sustained drug delivery devices. In order to overcome this low encapsulation efficiency, a W/0 single emulsion technique was developed and evaluated in an attempt to minimise the loss of the macromolecule into the continuous aqueous phase and increase encapsulation efficiency. Poly(lactide-co-glycolide) [PLCG] 75:25 and 50:50, PEA alone and PEA blended with PLCG 50:50 to accelerate biodegradation, were used to microencapsulate the water soluble antibiotic vancomycin, a putative replacement for gentamicin in the control of bacterial infection in orthopaedic surgery especially during total hip replacement. Spherical microspheres (17.39±6.89~m,n=74-56.5±13.8~m,n=70) were successfully fabricated with vancomycin loadings of 10, 25 and 50%, regardless of the polymer blend used. All microspheres remained structurally intact over the period of vancomycin release and exhibited high percentage yields( 40. 75±2 .86%- 97.16±4.3%,n=3)and encapsulation efficiencies (47.75±9.0%- 96.74±13.2%,n=12). PLCG 75:25 microspheres with a vancomycin loading of 50% were judged to be the most useful since they had an encapsulation efficiency of 96.74+13.2%, n=12 and sustained therapeutically significant vancomycin release (15-25μg/ml) for up to 26 days. This work has provided the means for the fabrication of a spectrum of prototype biodegradable microparticulates, whose biodegradation has been characterised in physiological media and which have the potential for the sustained delivery of therapeutically useful macromolecules including water soluble antibiotics for orthopaedic applications.

The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum.

Bioequivalence of sustained release theophylline formulations

The bioequivalence of sustained release theophylline formulations, marketed in the United Kingdom, has been investigated in relation to the co-administration of food in both single dose and steady state volunteer studies. The effect of food on pharmacokinetic parameters and their clinical relevance was researched. Experimentation using drug induced modification of gastric motility to ascertain the component influences of the rate of gastric emptying on the absorption of theophylline from sustained release formulations was conducted. Prolongation of time to maximum plasma theophylline concentration by food reported in the literature and its clinical importance was investigated in once daily compared with twice daily administration of sustained release theophylline formulations and smoking habit. The correlation between saliva and plasma theophylline concentrations as a means of developing a non-invasive sampling techniques was examined. Data obtained from in vitro dissolution studies was compared with in vivo results. This thesis has shown no significant differences occurred in the pharmacokinetic parameters measured between sustained release formulations available in the United Kingdom. The investigations into the influence of food on prolongation of time to maximum plasma theophylline concentration and other measured pharmacokinetic parameters demonstrated no important pharmacokinetic or clinical effects. Smoking adults taking sustained release theophylline formulations had similar drug clearances to those reported in the literature for smokers taking plain uncoated theophylline formulations. KEY WORDS Bioequivalence Theophylline Sustained Release Food Pharmacokinetics RONALD PURKISS SUBMITTED FOR

The impact of ageing on the barriers to drug delivery

Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery. © 2012 Elsevier B.V. All rights reserved.

Trigger release liposome systems:local and remote controlled delivery?

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

Relieving the first bottleneck in the drug discovery pipeline:using array technologies to rationalize membrane protein production

The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.

Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release

Ethosuximide is the drug of choice for treating generalized absence seizures, but its mechanism of action is still a matter of debate. It has long been thought to act by disrupting a thalamic focus via blockade of T-type channels and, thus, generation of spike-wave activity in thalamocortical pathways. However, there is now good evidence that generalized absence seizures may be initiated at a cortical focus and that ethosuximide may target this focus. In the present study we have looked at the effect ethosuximide on glutamate and GABA release at synapses in the rat entorhinal cortex in vitro, using two experimental approaches. Whole-cell patch-clamp studies revealed an increase in spontaneous GABA release by ethosuximide concurrent with no change in glutamate release. This was reflected in studies that estimated global background inhibition and excitation from intracellularly recorded membrane potential fluctuations, where there was a substantial rise in the ratio of network inhibition to excitation, and a concurrent decrease in excitability of neurones embedded in this network. These studies suggest that, in addition to well-characterised effects on ion channels, ethosuximide may directly elevate synaptic inhibition in the cortex and that this could contribute to its anti-absence effects. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Liposome formulation of poorly water soluble drugs:optimisation of drug loading and ESEM analysis of stability

Liposomes due to their biphasic characteristic and diversity in design, composition and construction, offer a dynamic and adaptable technology for enhancing drug solubility. Starting with equimolar egg-phosphatidylcholine (PC)/cholesterol liposomes, the influence of the liposomal composition and surface charge on the incorporation and retention of a model poorly water soluble drug, ibuprofen was investigated. Both the incorporation and the release of ibuprofen were influenced by the lipid composition of the multi-lamellar vesicles (MLV) with inclusion of the long alkyl chain lipid (dilignoceroyl phosphatidylcholine (C 24PC)) resulting in enhanced ibuprofen incorporation efficiency and retention. The cholesterol content of the liposome bilayer was also shown to influence ibuprofen incorporation with maximum ibuprofen incorporation efficiency achieved when 4 μmol of cholesterol was present in the MLV formulation. Addition of anionic lipid dicetylphosphate (DCP) reduced ibuprofen drug loading presumably due to electrostatic repulsive forces between the carboxyl group of ibuprofen and the anionic head-group of DCP. In contrast, the addition of 2 μmol of the cationic lipid stearylamine (SA) to the liposome formulation (PC:Chol - 16 μmol:4 μmol) increased ibuprofen incorporation efficiency by approximately 8%. However further increases of the SA content to 4 μmol and above reduced incorporation by almost 50% compared to liposome formulations excluding the cationic lipid. Environmental scanning electron microscopy (ESEM) was used to dynamically follow the changes in liposome morphology during dehydration to provide an alternative assay of liposome stability. ESEM analysis clearly demonstrated that ibuprofen incorporation improved the stability of PC:Chol liposomes as evidenced by an increased resistance to coalescence during dehydration. These finding suggest a positive interaction between amphiphilic ibuprofen molecules and the bilayer structure of the liposome. © 2004 Elsevier B.V. All rights reserved.

Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices

Big advances are being achieved in the design of new implantable devices with enhanced properties. For example, synthetic porous three-dimensional structures can mimic the architecture of the tissues, and serve as templates for cell seeding. In addition, polymeric nanoparticles are able to provide a programmable and sustained local delivery of different types of biomolecules. In this study novel alternative scaffolds with controlled bioactive properties and architectures are presented. Two complementary approaches are described. Firstly, scaffolds with nanogels as active controlled release devices incorporated inside the three-dimensional structure are obtained using the thermally induced phase separation (TIPS) method. Secondly, a novel coating method using the spraying technique to load these nanometric crosslinked hydrogels on the surface of two-dimensional (2D) and three-dimensional (3D) biodegradable scaffolds is described. The scanning electron microscopy (SEM) images show the distribution of the nanogels on the surface of different substrates and also inside the porous structure of poly-a-hydroxy ester derivative foams. Both of them are compared in terms of manufacturability, dispersion and other processing variables.

Bromocriptine:old drug, new formulation and new indication

Bromocriptine is an ergot alkaloid dopamine D receptor agonist that has been used extensively in the past to treat hyperprolactinaemia, galactorrhoea and Parkinsonism. It is known that hypothalamic hypodopaminergic states and disturbed circadian rhythm are associated with the development of insulin resistance, obesity and diabetes in animals and humans. When administered in the early morning at the start of the light phase, a new quick release (QR) formulation of bromocriptine appears to act centrally to reset circadian rhythms of hypothalamic dopamine and serotonin and improve insulin resistance and other metabolic abnormalities. Phase II and III clinical studies show that QR-bromocriptine lowers glycated haemoglobin by 0.6-1.2% (7-13 mmol/mol) either as monotherapy or in combination with other antidiabetes medications. Apart from nausea, the drug is well tolerated. The doses used to treat diabetes (up to 4.8 mg daily) are much lower than those used to treat Parkinson's disease and have not been associated with retroperitoneal fibrosis or heart valve abnormalities. QR-bromocriptine (Cycloset™) has recently been approved in the USA for the treatment of type 2 diabetes mellitus (T2DM). Thus, a QR formulation of bromocriptine timed for peak delivery in the early morning may provide a novel neurally mediated approach to the control of hyperglycaemia in T2DM. © 2010 Blackwell Publishing Ltd.

Future of contact lens usage

I was recently part of a small committee looking at higher qualifications in contact lens practice and the discussion turned to future technologies. There was mention of different materials and different applications of contact lenses. Drug delivery with contact lenses was discussed as this has been talked about in the literature for a while. The first paper I could find that talked about using contact lenses for drug delivery dates back over 40 years. There was a review paper in CLAE in 2008 that looked specifically at this too [1]. However, where are these products? Why are we not seeing them in the market place? Maybe the technology is not quite there yet, or maybe patents are prohibiting usage or maybe the market is not big enough to develop such products? We do have lenses on the market with slow release of lubricating agents but not therapeutic agents used for ocular or systemic conditions. Contact lenses with pathogen detectors may be part of our contact lens armoury of the future and again we can already see papers in the literature that have trialled this technology for glucose monitoring in diabetics or lactate concentration in the tear film. Future contact lenses may incorporate better optics based on aberration control and we see this starting to emerge with aspheric designs designed to minimise spherical aberration. Irregular corneas can be fitted with topography based designs and again this technology exists and is being used by some manufacturers in their designs already. Moreover, the topography based fitting of irregular corneas is certainly something we see a lot of today and CLAE has seen many articles related to this over the last decade or so. What about further into the future? Well one interesting area must the 3-dimensional contact lenses, or contact lenses with electronic devices built in that simulate a display screen. A little like the virtual display spectacles that are already sold by electronics companies. It does not take much of a stretch of the imagination to see a large electronic company taking this technology on and making it viable. Will we see people on the train watching movies on these electronic virtual reality contact lenses? I think we will, but when is harder to know.

α7 nicotinic receptor-mediated astrocytic gliotransmitter release:Aβ effects in a preclinical Alzheimer's mouse model

It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ), the toxic trigger for Alzheimer's disease (AD), interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT). The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline. © 2013 Pirttimaki et al.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery

Purpose: The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods: Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers (L-arginine and L-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results: Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79±3.24), fine particle dose (FPD) (14.42±1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86±0.24 μm. However, L-leucine was significantly superior in enhancing the aerosolization performance ( L-arginine:%FPF 27.61±4.49-26.57±1.85; FPD 12.40±0.99-19.54±0.16 μg and MMAD 2.18±0.35-2. 98±0.25 μm, L-leucine:%FPF 36.90±3.6-43.38±5. 6; FPD 18.66±2.90-21.58±2.46 μg and MMAD 2.55±0.03-3. 68±0.12 μm). Incorporating L-leucine (1.5%w/w) reduced the burst release (24.04±3.87%) of SF compared to unmodified formulations (41.87±2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o-cell lines, resulted in cell viability of 85.57±5.44 and 60.66±6.75%, respectively, after 72 h treatment. Conclusion:The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery. © Springer Science+Business Media, LLC 2011.