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Surface-eroding polymers are of significant interest for various applications in the field of controlled drug delivery. Poly(ethylene carbonate), as an example, offers little control over the rate of degradation and, thus, drug release, which usually conflicts with the requirements for long-acting medications. Here, we challenged an option to decelerate the degradation of poly(ethylene carbonate) in vitro and in vivo. When polymer films loaded with distinct antioxidants (vitamins) along with the model drugs leuprorelin and risperidone were incubated in superoxide radical solution and phagocyte culture, the mass loss and drug release from the delivery vehicle was a function of the type and dose of the utilized antioxidant. Once the polymer surface was "attacked" by reactive oxygen species, the antioxidants were released on demand quenching the polymer-degrading radicals. Accordingly, specific combinations of polymer and radical scavengers resulted in controlled release medications with an extended "life-time" of one month or longer, which is difficult to achieve for poly(ethylene carbonate) in the absence of antioxidants. A comparable degradation and drug release behavior was observed when antioxidant-loaded poly(ethylene carbonate) films were implanted in rats. Furthermore, linear correlations were obtained between the mass loss of the polymer films and the released fraction of drug (with slopes close to 1), a clear indication for the surface erosion of poly(ethylene carbonate) in vitro and in vivo. Overall, an addition of antioxidants to poly(ethylene carbonate)-based controlled drug delivery vehicles represents a reasonable approach to modify the performance of long-acting medications, especially when a "life time" of weeks to months needs to be achieved. Surface-eroding poly(ethylene carbonate) (PEC) is of significant interest for long-acting injectable formulations. However, PEC offers only little control over the rate of degradation and, thus, drug release kinetics. We describe an option to decelerate the degradation rate of PEC in vitro and in vivo. When polymer films loaded with distinct antioxidants along with model drugs were incubated in superoxide radical solution, phagocyte culture and implanted in rats, their mass loss and drug release was a function of the type and dose of the utilized antioxidant. Accordingly, specific combinations of polymer and radical scavengers resulted in controlled release medications with an extended "life-time" of one month or longer, which is difficult to achieve for PEC in the absence of antioxidants. Once a PEC-based drug delivery vehicle is approached by e.g. , phagocytes, which secret radicals to degrade the polymer, an on-demand release of the encapsulated antioxidant took place. Consequently, slower polymer degradation accompanied by a sustained release of co-embedded therapeutic agents was observed. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The dimensions of orifices found in aperture plates used for nebulization can be modified by thin polymer coatings with the aim to control the size distribution of the generated aerosol droplets. However, the stability of such polymer coatings on the surface of nebulizer membranes during aerosol generation has not been elucidated. Nebulizer membranes made of stainless steel were covered with a thin film of poly(chloro- p -xylylene) (~1 μm) in the presence or absence of a silane-based adhesion promoter. Thereby, the orifice cross-sections of the nebulizer membrane were reduced by ~50%, accompanied by a remarkable decline in droplet size. Upon continuous nebulization of aqueous test liquids, the droplet size generated by the nonconditioned (no silane), poly(chloro- p -xylylene)-coated membranes reverted to that of the uncoated nebulizer membrane within ~5 min. By contrast, no such rapid return of droplet size to "baseline" values was noticed for the silane-conditioned, poly(chloro- p -xylylene)-coated counterparts. Scanning electron microscopy exhibited significant polymer detachment from the orifices of the nonconditioned (no silane) membranes and thus confirmed the findings from laser diffraction. Overall, silane-based adhesion promoters can increase the persistence of poly(chloro- p -xylylene) coatings on nebulizer membranes during aerosol generation. [ABSTRACT FROM AUTHOR]

Large porous particles (LPPs) are well-known vehicles for drug delivery to the lungs. However, it remains uncertain whether or to which extent the in vitro drug release behavior of LPPs can be predictive of their in vivo performance (e.g., systemic exposure and therapeutic efficacy). With regard to this, three budesonide-loaded LPP formulations with identical composition but distinct in vitro drug release profiles were studied in vivo for their pharmacokinetic and pharmacodynamic behavior after delivery to rat lung, and finally, an in vitro/in vivo correlation (IVIVC) was established. All formulations reduced approximately 75% of the uptake by RAW264.7 macrophages compared with budesonide/lactose physical mixture and showed a drug release-dependent retention behavior in the lungs of rats. Likewise, the highest budesonide plasma concentration was measured for the formulation revealing the fastest in vitro drug release. After deconvolution of the plasma concentration/time profiles, the calculated in vivo drug release data were successfully utilized for a point-to-point IVIVC with the in vitro release profiles and the predictability of the developed IVIVC was acceptable. Finally, effective therapy was observed in an allergic asthma rat model for the sustained drug release formulations. Overall, the obtained in vitro results correlate well with the systemic drug exposure and the therapeutic performance of the investigated lung-delivered formulations, which can provide an experimental basis for IVIVC development in the pulmonary-controlled delivery system. Large porous particles (LPPs) are well-known vehicles for drug delivery to the lungs. However, it remains uncertain whether or to which extent the in vitro drug release behavior of LPPs can be predicted by their in vivo performance (e.g., systemic exposure and therapeutic efficacy). With regard to this, three budesonide-loaded PLGA-based LPP formulations with identical composition but distinct in vitro drug release profiles were studied in vivo for their pharmacokinetic and pharmacodynamic behavior, and finally, an in vitro/in vivo correlation (IVIVC) was established. It was demonstrated that the influence of the in vitro drug release profile was obvious during lung retention, systemic exposure, and therapeutic efficacy measurements. An IVIVC (Level A) was successfully established for the budesonide-loaded LPPs delivered to the airspace of rats for the first time. Taken together, the present work will clearly support research and development activities in the field of controlled drug delivery to the lungs. [ABSTRACT FROM AUTHOR]

Despite the significant interest in therapeutic antibodies for the treatment of airway diseases, no study addressed the challenge, which can arise when such formulations need to be made accessible for nebulization in concentrated (viscous) form. By (1) determining the maximum viscosity, which can still be atomized by vibrating-mesh technology and (2) supplementing the antibody formulation under investigation with at least 1 excipient, which decreases the viscosity under that specific threshold value of the utilized inhaler (and maintains the stability of the formulation), it should be possible to nebulize concentrated antibody formulations. Using sucrose as a viscosity enhancer, the viscosity threshold value amounted to ∼6 mPa*s for the eFlow®rapid device (output rate of <0.1 g/min). When a supplementation of a concentrated model antibody formulation (125 mg/mL) with specific amounts of lysine (≥50 mM) and arginine (≥20 mM) led to the desired drop in viscosity (to <5.5 mPa*s), the previously non-nebulizable formulation (no measurable aerosol output) was made accessible for vibrating-mesh nebulization (output rate of up to ∼0.5 g/min, droplet diameter of <5 μm). The stability of the current antibody formulation was not adversely affected when nebulized in the presence of lysine and arginine. Overall, the presented results will help increase the understanding on how to aerosolize concentrated protein formulations by vibrating-mesh technology. [ABSTRACT FROM AUTHOR]

Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field. [ABSTRACT FROM AUTHOR]

The size of airborne particles determines their deposition pattern within the lungs and therefore, the efficacy of inhalation therapy. The present study analyzed factors affecting liquid atomization performed by vibrating-membrane technology. First, the process of vibrating-membrane nebulization (eFlow®rapid and Aeroneb® Pro) was challenged with numerous inorganic salts and active pharmaceutical ingredients. All investigated samples caused a sigmoidal decrease in aerosol droplet size upon an increase in concentration. Calculated dose-effect curve characteristics (i.e., half maximal effective sample concentration inducing a halfway drop of the droplet size) indicated distinct molar “potency” amongst the utilized samples with respect to generation of “adequate” inhalation aerosols. Second, the employed solvent (aqueous vs. organic) was shown to amplify the electrolyte effect on vibrating-membrane technology (i.e., dose-effect curve characteristics and overall aerosol droplet size). Third, besides the sample and solvent type, the nozzle composition (diverse metal and polymer coatings) induced a strong impact on the current mode of nebulization. Here, coating materials were identified, which necessitated higher and lower electrolyte concentrations in order to decrease the aerosol droplet size in comparable manner to plain nebulizer membranes. Thus, depending on the employed sample type and concentration, solvent and nozzle composition, a delivery of “inadequate” or “adequate” aerosols for inhalation purpose was observed. Overall, the current observations could be used to compile suggestions for the rational design of aerosol formulations and nebulizer devices meeting the specific requirements for successful inhalation therapy. [ABSTRACT FROM AUTHOR]

The performance of vibrating membrane technology (i.e., aerosol droplet size and output rate) depends on the specific electrolyte concentration. However, the underlying factors, which determine nebulizer performance, are currently only poorly understood. This study compared the charge of aerosol droplets (Dekati ® BOLAR ™ ) nebulized with the eFlow ® rapid and the streaming potential (SurPASS ® ) forming at the liquid/metal interface. Nebulization of 0.01 mM sodium chloride resulted in a rather large droplet size of >8 μm and an output rate of only ∼0.4 g/min. Increasing the sodium chloride content to 10 mM led to a droplet size of <5 μm and an output rate of ∼1.0 g/min. No significant difference was detected when comparing the net charge-to-mass ratios of generated aerosols. In contrast, the streaming potential (i.e., adversary of droplet detachment) differed remarkably between the 2 electrolyte solutions. The higher salt concentration compensated the electrical potential difference formed at the liquid/metal interface and, thus, caused an increased output rate (and a delivery of smaller aerosol droplets). Overall, this study identified the streaming potential as a significant parameter with impact on vibrating membrane nebulizer performance. The presented results will promote progress in this specific subfield of aerosol drug delivery. [ABSTRACT FROM AUTHOR]

Colloidal drug delivery systems often face physical and chemical instability as well as challenges with directed delivery. In order to overcome these challenges the colloidal formulations can be processed into microparticulate form (nanoembedded microparticles (NEMs)). In this study, different polymer nanocarriers (poly(lactide- co -glycolide), poly(styrene), chitosan and dendrimers) were used for preparing NEMs by spray-drying. Further, distinct matrix excipients were investigated including sugars (i.e., trehalose, sucrose, mannitol) and polymers (poly(vinyl pyrrolidone) and poly(ethylene glycol)), and the characteristics and performance of NEMs were studied in detail. It was found that with increasing hydrophilicity of the polymer nanocarriers, an increasing amount of excipient was necessary to stabilize the nanoparticles. NEMs containing polyplexes and nanogels required a matrix-to-nanoparticle (M:N) ratio of 50:1 and 10:1, respectively, whereas NEMs with poly(styrene) and poly(lactide- co -glycolide) only required an M:N ratio of 1:1 and 1:4, respectively. Investigation of different excipients demonstrated that water soluble sugars and polymers can be used to prepare NEMs and that spray-dried amorphous excipients (trehalose, sucrose, poly(vinyl pyrrolidone)) are superior to spray-dried crystalline excipients (mannitol, poly(ethylene glycol)) for stabilizing NEMs. It is therefore important to select an appropriate excipient for stabilization of a given nanoparticle system and identify a suitable level of this excipient to keep the nanoparticles viable. [ABSTRACT FROM AUTHOR]

Direct vasodilator delivery to the airways enables a selective therapy of pulmonary hypertension (PH). However, short-term effects of the applied medication require multiple daily inhalations. Controlled release formulations (polymeric nanomedicines) offer the potential of prolonging drug effects within the respiratory tract, thereby reducing the number of necessary inhalations. In the model of U46619-elicited PH, sildenafil and two sildenafil-loaded polymeric submicron particle formulations were evaluated for their pharmacodynamic and pharmacokinetic characteristics and acute tolerability. Lung-delivered sildenafil caused a selective dose-dependent decline of the pulmonary arterial pressure and vascular resistance. Compared to the transient pharmacodynamic effect observed for sildenafil, the same dose of nanoencapsulated sildenafil resulted in prolongation, but not augmentation, of the pulmonary vasodilatation. An extended pharmacokinetic profile was observed for nanoencapsulated sildenafil, and nanomedicines revealed no acute toxicity. The amplification of pulmonary vasodilatory response caused by nanoencapsulation of sildenafil offers an intriguing approach to ameliorate the therapy of PH. From the Clinical Editor Pulmonary hypertension usually results in right heart failure long term. Current medical therapy includes the use of potent vasodilators such as sildenafil. In this article, the authors investigated the use of nanoencapsulated formulation for sustained delivery via inhalation route. An extended pharmacokinetic profile was seen for this nanoformulation with little side effects. It is hoped that clinical application of this would come to fruition soon. [ABSTRACT FROM AUTHOR]

The current study describes a convenient method for a direct size classification of spray-dried powders, which is of general interest for diverse applications in drug delivery. Accordingly, the time-consuming “trial-and-error” approach to identify critical formulation and process parameters influencing the final product specifications is replaced by a final fractionation step of the dried particles by inertial impaction. When employing the “original” vibrational spray-dryer (i.e., Nano Spray-Dryer B-90, Büchi) it was evident that both the liquid feed characteristics (e.g., concentration of dissolved solids) and process parameters (e.g., nozzle type and spray-rate) significantly affected the particle size and size distribution of generated sildenafil-loaded poly(lactide- co -glycolide) microparticles (particle size: ~ 4–~ 11 μm; particle size distribution ( span ): ~ 1.3–~ 2.2). The said formulations showed prolonged in vitro drug release properties with mean dissolution times (MDTs) ranging between ~ 4 and ~ 14 h. By contrast, replacing the electrostatic particle collector of the vibrational spray-dryer by a Next Generation Impactor enabled a direct size classification of spray-dried microparticles according to their aerodynamic behavior. Formulations collected from the individual impactor stages exhibited a defined particle size (i.e., stages I, II, III and IV with 7.8, 4.5, 3.0 and 2.1 μm, respectively) and were significantly narrowly distributed ( span : ≤ 1.2) than the non-fractionated controls. Likewise, fractionated formulations were characterized by a sustained sildenafil in vitro release behavior (MDT: ~ 1.5–~ 7 h). Overall, regardless of the primary particle size and size distribution of spray-dried powders, desired size characteristics can be achieved by a terminal size classification by inertial impaction. Hence, the described approach provides spray-dried products meeting the specific requirements of the intended application (e.g., prolonged drug delivery to the lungs). [ABSTRACT FROM AUTHOR]

Following systemic administration polymeric drug delivery vehicles allow for a controlled and targeted release of the encapsulated medication at the desired site of action. For an elevated and organ specific accumulation of their cargo, nanocarriers need to avoid opsonization, activation of the complement system and uptake by macrophages of the mononuclear phagocyte system. In this respect, camouflaged vehicles revealed a delayed elimination from systemic circulation and an improved target organ deposition. For instance, a steric shielding of the carrier surface by poly(ethylene glycol) substantially decreased interactions with the biological environment. However, recent studies disclosed possible deficits of this approach, where most notably, poly(ethylene glycol)-modified drug delivery vehicles caused significant immune responses. At present, identification of novel potential carrier coating strategies facilitating negligible immune reactions is an emerging field of interest in drug delivery research. Moreover, physical carrier properties including geometry and elasticity seem to be very promising design attributes to surpass numerous biological barriers, in order to improve the efficacy of the delivered medication. [ABSTRACT FROM AUTHOR]

The current study investigated the mechanisms involved in the process of biophysical inhibition of pulmonary surfactant by polymeric nanoparticles (NP). The minimal surface tension of diverse synthetic surfactants was monitored in the presence of bare and surface-decorated (i.e. poloxamer 407) sub-100 nm poly(lactide) NP. Moreover, the influence of NP on surfactant composition (i.e. surfactant protein (SP) content) was studied. Dose-elevations of SP advanced the biophysical activity of the tested surfactant preparation. Surfactant-associated protein C supplemented phospholipid mixtures (PLM-C) were shown to be more susceptible to biophysical inactivation by bare NP than phospholipid mixture supplemented with surfactant protein B (PLM-B) and PLM-B/C. Surfactant function was hindered owing to a drastic depletion of the SP content upon contact with bare NP. By contrast, surface-modified NP were capable of circumventing unwanted surfactant inhibition. Surfactant constitution influences the extent of biophysical inhibition by polymeric NP. Steric shielding of the NP surface minimizes unwanted NP–surfactant interactions, which represents an option for the development of surfactant-compatible nanomedicines. [ABSTRACT FROM AUTHOR]

Nebulization of active pharmaceutical ingredient ( API) solutions is a well-established means to achieve pulmonary drug deposition. The current study identified the impact of formulation variables on the aerosolization performance of the eFlow®rapid with special respect to optimized lung application. API formulations (including excipient-supplemented samples) were investigated for physicochemical properties, then nebulized using vibrating-mesh technology. The generated aerosol clouds were analyzed by laser diffraction. Aerosol deposition characteristics in the human respiratory tract were estimated using an algebraic model. Remarkable effects on aerosolization performance [i.e., mass median aerodynamic diameter ( MMAD)] of API solutions were obtained when the sample conductivity (by API concentration and type, sodium chloride addition) and dynamic viscosity (by application of sucrose and poly(ethylene glycol) 200) were elevated. A similar influence was observed for a decline in surface tension (by ethanol addition). Thus, a defined adjustment of formulation parameters allowed for a decrease of the MMAD from ∼8.0 μm to values as small as ∼3.5 μm. Consequently, the pattern and efficiency of aerosol deposition in the human respiratory tract were improved. In conclusion, identification of physicochemical variables and their way of influencing vibrating-mesh nebulization has been provided to deliver a platform for tailoring aerosol characteristics and thus, advancing pulmonary therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2585-2589, 2014 [ABSTRACT FROM AUTHOR]

Abstract: Nanomedicine comprises a significant potential to approach the therapy of severe diseases. Knowledge of nanoparticle behavior at the target site would contribute to the development of specialized tools for respiratory medicine. Here, we were interested in the potential of micro-computed tomography (μCT) imaging to monitor the pulmonary distribution of polymeric nanoparticles. Composite nanoparticles were analyzed for physicochemical properties, morphology and composition. μCT was employed to visualize the pulmonary distribution of composite nanoparticles in an ex vivo lung model. Employed composite nanoparticles were composed of poly(styrene) cores coated by a thin shell of colloidal iron oxide. Particles were mainly located in the interstitial space and associated with pulmonary cells, as observed by light microscopy. μCT detected enhanced X-ray opacities in the conducting (linear pattern) and respiratory airways (aciniform X-ray attenuations). In conclusion, multifunctional nanoparticles will prompt the development of novel therapeutic and diagnostic tools in respiratory medicine. [Copyright &y& Elsevier]

Abstract: Polymeric nanoparticles meet the increasing interest for drug delivery applications and hold great promise to improve controlled drug delivery to the lung. Here, we present a series of investigations that were carried out to understand the impact of formulation variables on the nebulization performance of novel biodegradable sildenafil-loaded nanoparticles designed for targeted aerosol therapy of life-threatening pulmonary arterial hypertension. Narrowly distributed poly(d,l-lactide-co-glycolide) nanoparticles (size: ∼200nm) were prepared by a solvent evaporation technique using poly(vinyl alcohol) (PVA) as stabilizer. The aerodynamic and output characteristics using the Aeroneb® Pro nebulizer correlated well with the dynamic viscosity of the employed fluids for nebulization. The nebulization performance was mainly affected by the amount of employed stabilizer, rather than by the applied nanoparticle concentration. Nanoparticles revealed physical stability against forces generated during aerosolization, what is attributed to the adsorbed PVA layer around the nanoparticles. Sildenafil was successfully encapsulated into nanoparticles (encapsulation efficiency: ∼80%). Size, size distribution and sildenafil content of nanoparticles were not affected by nebulization and the in vitro drug release profile demonstrated a sustained sildenafil release over ∼120min. The current study suggests that the prepared sildenafil-loaded nanoparticles are a promising pharmaceutical for the therapy of pulmonary arterial hypertension. [Copyright &y& Elsevier]

Abstract: Amphiphilic PEG–PCL–PEI triblock copolymers self-assemble into nano-scaled, positively charged, multifunctional carriers, suitable for drug and gene delivery. A set of block copolymers with varying hydrophilic/hydrophobic ratio (systematically altered at the borderline of micelle and particle forming polymers) was synthesized, characterized and assembled into carriers. A detailed structural characterization in the liquid state of these assemblies was carried out: carrier size was determined using dynamic light scattering, cryogenic scanning electron microscopy and atomic force microscopy. Nuclear magnetic resonance analyses elucidated carrier’s core–shell structure. ζ-potential and thickness of the hydrophilic outer polymer shell were determined by laser Doppler anemometry. Subsequently the impact of carrier’s structure on its features (stability and toxicity) was investigated. Polymers hydrophilic in nature formed small (<40 nm) micelle-like carriers, whilst hydrophobic polymers aggregated to larger particle-like assemblies (>100 nm). Monitoring carrier size as a function of initial polymer concentration clarified different assembly mechanisms. Shell thickness, colloidal stability and toxicity were found to depend on the length of the hydrophilic polymer block. Due to controllable size, charge, stability and toxicity, this class of novel carriers is a promising candidate for prospective co-delivery of drugs and nucleic acids. [Copyright &y& Elsevier]

Abstract: Nanoparticulate drug carriers have been proposed for the targeted and controlled release of pharmaceuticals to the lung. However, inhaled particles may adversely affect the biophysical properties of pulmonary surfactant. This study examines the influence of polymeric nanoparticles with distinct physicochemical properties on the adsorption and dynamic surface tension lowering properties of pulmonary surfactant. Nanoparticles had a mean size of 100 nm with narrow size distributions. Although poly(styrene) and poly(D,L-lactide-co-glycolide) nanoparticles revealed a dose-dependent influence on biophysics of pulmonary surfactant, positively-charged nanoparticles made from poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) showed no effect. This behavior is attributed to the differences in ζ-potential and surface hydrophobicity, which in turn involves an altered adsorption pattern of the positively charged surfactant proteins to the nanoparticles. This study suggests that polymeric nanoparticles do not substantially affect the biophysical properties of pulmonary surfactant and may be a viable drug-delivery vehicle for the inhalative treatment of respiratory diseases. From the Clinical Editor: Inhaled nanoparticulate drug carriers may adversely affect the biophysical properties of pulmonary surfactant. In this study the influence of polymeric nanoparticles was characterized from this standpoint, with the conclusion that polymeric nanoparticles do not substantially affect the biophysical properties of pulmonary surfactant and may be viable drug-delivery vehicles for inhalational treatment. [Copyright &y& Elsevier]

Abstract: The use of colloidal carrier systems for pulmonary drug delivery is an emerging field of interest in nanomedicine. The objective of this study was to compare the pulmonary absorption and distribution characteristics of the hydrophilic model drug 5(6)-carboxyfluorescein (CF) after aerosolization as solution or entrapped into nanoparticles in an isolated rabbit lung model (IPL). CF-nanoparticles were prepared from a new class of biocompatible, fast degrading, branched polyesters by a modified solvent displacement method. Physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, stability of nanoparticles to nebulization, aerosol characteristics as well as pulmonary dye absorption and distribution profiles after nebulization in an IPL were investigated. CF-nanoparticles were spherical in shape with a mean particle size of 195.3±7.1nm, a polydispersity index of 0.225±0.017 and a ζ-potential of −28.3±0.3mV. Encapsulation efficiencies of CF were as high as about 60% (drug loading of 3% (w/w)); 90% of the entrapped CF were released during the first 50min in vitro. Nanoparticle characteristics were not significantly affected by the aerosolization process utilizing a vibrating mesh nebulizer. After deposition of equal amounts of CF in the IPL, less CF was detected in the perfusate for CF-nanoparticles (plateau concentration 9.2±2.4ng/ml) when compared to CF aerosolized from solution (17.7±0.8ng/ml). In conclusion, the data suggest that inhalative delivery of biodegradable nanoparticles may be a viable approach for pulmonary drug delivery. Moreover, a targeting effect to the lung tissue is claimed. [Copyright &y& Elsevier]