Foreign Particulates Research Articles

Mucosal Penetrative Polymeric Micelle Formulations for Insulin Delivery to the Respiratory Tract.

Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers. We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract. The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h. This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.

The effect of yaw damper performance degradation on carbody hunting of high-speed trains

The yaw damper is an integral and pivotal component in guaranteeing the carbody hunting stability of high-speed trains (HSTs). However, it is reported that the occurring incidences of low-frequency carbody hunting frequently have been observed in HSTs, a predicament attributed to the degradation of yaw damper performance resulting from the obstruction of the damping valve by foreign particulates. Given these circumstances, the objective of this study is to investigate the impact of yaw damper performance degradation on the intricate phenomenon of carbody hunting motion. A HST dynamic model is developed, incorporating a detailed physical parameter model of the yaw damper, which enables the reproduction of abnormal low-frequency swaying arising from the deterioration in yaw damper performance. The findings of this study demonstrate that the obstruction of the damping valve significantly augments the damping force and dynamic stiffness of the yaw damper, thereby potentially instigating the occurrence of severe low-frequency hunting motion and consequent deterioration in the ride comfort of HSTs.

Evaluation of nasal mucociliary clearance time in children with celiac disease

ObjectivesCeliac disease is an autoimmune disorder that develops because of sensitivity to gluten-containing grains in genetically disposed individuals. Nasal mucociliary clearance is the most important protective factor that protects the upper and lower airways from foreign particulates. This study aimed to investigate the effect of celiac disease on nasal mucociliary clearance. MethodsThe study included patients with celiac disease and healthy children. Nasal mucociliary clearance time was measured using the saccharin test. The children's saccharin taste time was recorded in seconds. ResultsOverall, 65 children were included: 43 patients with celiac disease (66.2%) and 22 healthy children (33.8%). Of all the children, 42 (64.6%) were female, and the average age was 11.8 ± 4 years. Nasal mucociliary clearance time of patients with celiac disease (531 ± 155 s) was significantly prolonged in comparison to that of healthy children (448 ± 80 s) (p = 0.006). No relationships were found between the diagnosis age, celiac type, and histopathological phase and compliance with the gluten-free diet and nasal mucociliary clearance time of patients with celiac disease. ConclusionsThis study showed that nasal mucociliary clearance was prolonged in patients with celiac disease. A defect in nasal mucociliary clearance increases the risk of infection and inflammation in small airways. Studies reported a high prevalence of respiratory tract infection in patients with celiac disease, which was associated with malnutrition, vitamin deficiency, and hyposplenism. The findings of the present study indicated that impairment of nasal mucociliary clearance could play a role in the development of frequent lung infections in patients with celiac disease.

Spatial Mapping of Tracheal Ciliary Beat Frequency Using Real Time Phase-Resolved Doppler Spectrally Encoded Interferometric Microscopy

Ciliary motion in the upper airway is the primary mechanism by which the body transports foreign particulates out of the respiratory system in order to maintain proper respiratory function. The ciliary beating frequency (CBF) is often disrupted with the onset of disease as well as other conditions, such as changes in temperature or in response to drug administration. Current imaging of ciliary motion relies on microscopy and high-speed cameras, which cannot be easily adapted to in-vivo imaging. M-mode optical coherence tomography (OCT) imaging is capable of visualization of ciliary activity, but the field of view is limited. We report on the development of a spectrally encoded interferometric microscopy (SEIM) system using a phase-resolved Doppler (PRD) algorithm to measure and map the ciliary beating frequency within an en face region. This novel high speed, high resolution system allows for visualization of both temporal and spatial ciliary motion patterns as well as propagation of metachronal wave. Rabbit tracheal CBF ranging from 9 to 13 Hz has been observed under different temperature conditions, and the effects of using lidocaine and albuterol have also been measured. This study is the stepping stone to in-vivo studies and the translation of imaging spatial CBF to clinics.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

Acetylcholine-induced Ciliary Beat of the Human Nasal Mucosa Is Regulated by the Pannexin-1 Channel and Purinergic P2X Receptor.

These results indicate that the regulatory mechanism of the Ach-induced ciliary beat is dependent on extracellular Ca2+ and involves the muscarinic Ach receptor, IP3 receptor, pannexin-1 channel, purinergic P2X receptor, and connexin channel. We proposed a tentative intracellular signaling pathway of the Ach-induced ciliary beat, in which the pannexin-1-P2X unit may play a central role in ciliary beat regulation.

Influence of membrane surface charge on adsorption of complement proteins onto supported lipid bilayers

The complement system is an important part of the innate immune response, and there is great interest in understanding how complement proteins interact with lipid membrane interfaces, especially in the context of recognizing foreign particulates (e.g., liposomal nanomedicines). Herein, a supported lipid bilayer platform was employed in order to investigate the effect of membrane surface charge (positive, negative, or neutral) on the adsorption of three complement proteins. Quartz crystal microbalance-dissipation (QCM-D) experiments measured the real-time kinetics and total uptake of protein adsorption onto supported lipid bilayers. The results demonstrate that all three proteins exhibit preferential, mainly irreversible adsorption onto negatively charged lipid bilayers, yet there was also significant variation in total uptake and the relative degree of adsorption onto negatively charged bilayers versus neutral and positively charged bilayers. The total uptake was also observed to strongly depend on the bulk protein concentration. Taken together, our findings contribute to a broader understanding of the factors which influence adsorption of complement proteins onto lipid membranes and offer guidance towards the design of synthetic lipid bilayers with immunocompetent features.

Gas-Phase Surface Engineering of Polystyrene Beads Used to Challenge Automated Particle Inspection Systems

Container challenge sets, used in the qualification and validation of automated visible particle inspection systems in the parenteral drug industry, are prepared by seeding a single standardized polystyrene-divinylbenzene (PS-DVB) bead inside the commercial product to mimic foreign particulates. Because of its low surface energy and wettability, the bead adheres to container walls, hindering its detection by the motion-based inspection system. The aim of this research is to modify the surface properties of the bead in such a way that it repulses the inner walls and stays in suspension inside the liquid product. The surface treatment consists of a photoinduced chemical vapor deposition (PICVD) process using syngas and ultraviolet (UVC) light. Following treatment, newly grafted C–OH, C–O–C, C═O, and COOH functional groups on the bead’s surface are observed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, leading to an increase in the surface energy from 31 ± 1 to 65 ± 2 mJ/m2...

Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes.

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.

Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex Vivo and Distribution in Vivo.

Achieving sustained drug delivery to mucosal surfaces is a major challenge due to the presence of the protective mucus layer that serves to trap and rapidly remove foreign particulates. Nanoparticles engineered to rapidly penetrate mucosal barriers (mucus-penetrating particles, "MPP") have shown promise for improving drug distribution, retention and efficacy at mucosal surfaces. MPP are densely coated with polyethylene glycol (PEG), which shields the nanoparticle core from adhesive interactions with mucus. However, the PEG density required to impart the "stealth" properties to nanoparticles in mucus, and thus, uniform distribution in vivo, is still unknown. We prepared biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a range of PEG surface densities by blending various ratios of a diblock copolymer of PLGA and 5 kDa poly(ethylene glycol) (PLGA-PEG5k) with PLGA. We then evaluated the impact of PEG surface density, measured using an (1)H NMR method, on mucin binding in vitro, nanoparticle transport in freshly obtained human cervicovaginal mucus (CVM) ex vivo, and nanoparticle distribution in the mouse cervicovaginal tract in vivo. We found that at least 5% PEG was required to effectively shield the nanoparticle core from interacting with mucus components in vitro and ex vivo, thus leading to enhanced nanoparticle distribution throughout the mouse vagina in vivo. We then demonstrated that biodegradable MPP could be formulated from blends of PLGA and PLGA-PEG polymers of various molecular weights, and that these MPP provide tunable drug loading and drug release rates and durations. Overall, we describe a methodology for rationally designing biodegradable, drug-loaded MPP for more uniform delivery to the vagina.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Biomimetic and synthetic interfaces to tune immune responses.

Organisms depend upon complex intercellular communication to initiate, maintain, or suppress immune responses during infection or disease. Communication occurs not only between different types of immune cells, but also between immune cells and nonimmune cells or pathogenic entities. It can occur directly at the cell-cell contact interface, or indirectly through secreted signals that bind cell surface molecules. Though secreted signals can be soluble, they can also be particulate in nature and direct communication at the cell-particle interface. Secreted extracellular vesicles are an example of native particulate communication, while viruses are examples of foreign particulates. Inspired by communication at natural immunological interfaces, biomimetic materials and designer molecules have been developed to mimic and direct the type of immune response. This review describes the ways in which native, biomimetic, and designer materials can mediate immune responses. Examples include extracellular vesicles, particles that mimic immune cells or pathogens, and hybrid designer molecules with multiple signaling functions, engineered to target and bind immune cell surface molecules. Interactions between these materials and immune cells are leading to increased understanding of natural immune communication and function, as well as development of immune therapeutics for the treatment of infection, cancer, and autoimmune disease.

Comparison of Some Physicochemical Properties of Locust Bean Seeds Gum Extracted by Acid and Water Pre-Treatments

In this research, locust bean gums were removed from seeds with different extraction methods and some physicochemical properties were analyzed for gums and also locust beans. Three different extractions were treated at different temperatures and durations of sulfuric acid (H2SO4, 60%) solution, hydrochloric acid (HCl, 30%) solution and boiling water. Following dehulling and drying processes, seeds were milled and locust bean gums (LBG) were obtained eventually. The color values, moisture, protein, ash, sugar, pH, total acidity, soluble solids content, foreign particulates, acid insoluble ash contents and viscosity curves were compared for all samples. The results exhibited that the highest ash (1.94%) and protein (6.65%) contents were determined by water extraction gum, the highest acid-insoluble ash (3.58%) and foreign particulates (44.17%) contents were determined by HCl extraction gum. The lowest protein (5.01%), acid insoluble ash (1.29%), the foreign particulates (34.99%) and the highest viscosity value (533.9 mPas) were found from H2SO4 extraction gum. The results of investigation also showed that the H2SO4 extraction method was found to be more appropriate than HCl and water extraction methods to obtain a good quality gum.

EVALUATION AND QUALITY CONTROL OF NASAL SPRAY

Nasal drug delivery has now been recognized as a very promising route for delivery of therapeutic compounds including biopharmaceuticals. This route is also advisable for drugs undergoing extensive first pass effect. The present article highlights the evaluation parameters of nasal spray, suspension, and solutions. While formulating the nasal drug delivery formulations various parameters are to be consider such as Appearance, Color, and Clarity, Identification, Drug content (Assay), Impurities and Degradation Products, Preservative(s) and Stabilizing Excipient(s) Assay, Pump Delivery, Spray content uniformity, Spray Content Uniformity (SCU) through Container Life, Spray Pattern and Plume Geometry, Droplet Size Distribution, Particle size distribution (suspension), Microscopic Evaluation (Suspensions), Foreign Particulates, Microbial limit, Preservative Effectiveness, Net Content and Weight Loss (Stability), Leachables (Stability), PH, Osmolality.  Key words: Nasal spray, Evaluation, Quality control, Drug delivery system.

A multi-parametric particle-pairing algorithm for particle tracking in single and multiphase flows

Multiphase flows (MPFs) offer a rich area of fundamental study with many practical applications. Examples of such flows range from the ingestion of foreign particulates in gas turbines to transport of particles within the human body. Experimental investigation of MPFs, however, is challenging, and requires techniques that simultaneously resolve both the carrier and discrete phases present in the flowfield. This paper presents a new multi-parametric particle-pairing algorithm for particle tracking velocimetry (MP3-PTV) in MPFs. MP3-PTV improves upon previous particle tracking algorithms by employing a novel variable pair-matching algorithm which utilizes displacement preconditioning in combination with estimated particle size and intensity to more effectively and accurately match particle pairs between successive images. To improve the method's efficiency, a new particle identification and segmentation routine was also developed. Validation of the new method was initially performed on two artificial data sets: a traditional single-phase flow published by the Visualization Society of Japan (VSJ) and an in-house generated MPF data set having a bi-modal distribution of particles diameters. Metrics of the measurement yield, reliability and overall tracking efficiency were used for method comparison. On the VSJ data set, the newly presented segmentation routine delivered a twofold improvement in identifying particles when compared to other published methods. For the simulated MPF data set, measurement efficiency of the carrier phases improved from 9% to 41% for MP3-PTV as compared to a traditional hybrid PTV. When employed on experimental data of a gas–solid flow, the MP3-PTV effectively identified the two particle populations and reported a vector efficiency and velocity measurement error comparable to measurements for the single-phase flow images. Simultaneous measurement of the dispersed particle and the carrier flowfield velocities allowed for the calculation of instantaneous particle slip velocities, illustrating the algorithm's strength to robustly and accurately resolve polydispersed MPFs.

Filters in pharmaceuticals: Automating the characterisation of foreign particulates

Counting and classifying foreign particulate materials on filters is essential in pharmaceutical manufacturing. Traditional techniques are lengthy and difficult. Ulf Willén of Malvern Instruments describes an automated method for improved statistical sampling.

Acoustic particulates density sensor

A technique for determining particulate density in a fluid monitors the changes in the speed of sound. Since the speed of sound is intimately related to the composites of the air mixture and since the speed of sound of clean air at any temperature and humidity can be calculated exactly, it is possible to estimate the density of any foreign particulates in the air by observing changes in the speed of sound. Formulations are derived that correlate the change in the speed of sound of the air mixture to their density fluctuations, thus allowing people to estimate the mass density of foreign particulates under any temperature and humidity. Alternatively, the change in density of the air mixture can be detected, thereby indicating the presence of contaminants and a possible alarm, even if the contaminants are not yet identified.

Quantifying rat pulmonary intravascular mononuclear phagocytes.

Cells of the mononuclear phagocyte system (MPS) protect the host by clearing effete and foreign particulates from the circulation. The current study was designed to identify, quantify, harvest, and provide a partial functional characterization of the systemic host-defense cell located in the pulmonary microvasculature of the rat. Critical colloid doses of test particulates (monastral blue B [MBB] or polystyrene beads) were infused intra-arterially into anesthetized rats so that phagocytically active pulmonary intravascular phagocytes could be identified. Morphologic characterization of in situ phagocytes was performed using electron microscopy. The number of active phagocytes was then determined using tissue samples processed for light microscopy. Finally, sequential perfusion of the pulmonary vasculature with buffer, chelating agent, and collagenase allowed elution and preliminary functional characterization of the pulmonary intravascular mononuclear phagocyte (PIMP). Electron microscopy demonstrated that both mononuclear phagocytes and neutrophils contributed to pulmonary sequestration of circulating particulates. Light microscopy showed that the microvasculature of each alveolus contained 0.50+/-0.19 active mononuclear phagocytes and 0.14+/-0.12 active neutrophils. A chelation/collagenase elution technique was then used to harvest the PIMP. Histologic evaluation of the postperfusion lungs indicated that 80% of the active phagocytes were removed by the technique. In total, the elution fluids contained 2.63+/-1.04 x 10(7) cells, with 1.60+/-0.78 x 10(7), 0.49+/-0.17 x 10(7), and 0.54+/-0.26 x 10(7) of those cells being mononuclear phagocytes, neutrophils, and lymphocytes, respectively. Functionally, the mononuclear phagocyte population exhibited a spectrum of phagocytic activities, with 51.5+/-19.5% of the cells being inactive, 33.9+/-13.4% exhibiting moderate phagocytic activity, and 14.6+/-9.8% demonstrating intensive phagocytic capacity. The current study provides the first quantified demonstration that mononuclear phagocytes are primarily responsible for sequestering blood-borne foreign particulates in the pulmonary circulation of the rat. Approximately 2 x 10(7) PIMP existed in the lungs of 300 gram rats. The functionally heterogeneous mononuclear phagocytes exhibited phagocytic capacities ranging from avidly phagocytic (14.6+/-9.8%) through moderately active (33.9+/-13.4%) to inactive. The lung microvasculature's large pool of inactive mononuclear phagocytes may provide a recruitable mechanism to allow significant increases in clearance of circulating particulates. A resident pool of activatable mononuclear phagocytes might explain previous clinical observations of increased particulate localization in the lung microvasculature of septic patients.

Quantifying rat pulmonary intravascular mononuclear phagocytes

Cells of the mononuclear phagocyte system (MPS) protect the host by clearing effete and foreign particulates from the circulation. The current study was designed to identify, quantify, harvest, and provide a partial functional characterization of the systemic host-defense cell located in the pulmonary microvasculature of the rat. Critical colloid doses of test particulates (monastral blue B [MBB] or polystyrene beads) were infused intra-arterially into anesthetized rats so that phagocytically active pulmonary intravascular phagocytes could be identified. Morphologic characterization of in situ phagocytes was performed using electron microscopy. The number of active phagocytes was then determined using tissue samples processed for light microscopy. Finally, sequential perfusion of the pulmonary vasculature with buffer, chelating agent, and collagenase allowed elution and preliminary functional characterization of the pulmonary intravascular mononuclear phagocyte (PIMP). Electron microscopy demonstrated that both mononuclear phagocytes and neutrophils contributed to pulmonary sequestration of circulating particulates. Light microscopy showed that the microvasculature of each alveolus contained 0.50 ± 0.19 active mononuclear phagocytes and 0.14 ± 0.12 active neutrophils. A chelation/ collagenase elution technique was then used to harvest the PIMP. Histologic evaluation of the postperfusion lungs indicated that 80% of the active phagocytes were removed by the technique. In total, the elution fluids contained 2.63 ± 1.04 × 107 cells, with 1.60 ± 0.78 × 107, 0.49 ± 0.17 × 107, and 0.54 ± 0.26 × 107 of those cells being mononuclear phagocytes, neutrophils, and lymphocytes, respectively. Functionally, the mononuclear phagocyte population exhibited a spectrum of phagocytic activities, with 51.5 ± 19.5% of the cells being inactive, 33.9 ± 13.4% exhibiting moderate phagocytic activity, and 14.6 ± 9.8% demonstrating intensive phagocytic capacity. The current study provides the first quantified demonstration that mononuclear phagocytes are primarily responsible for sequestering blood-borne foreign particulates in the pulmonary circulation of the rat. Approximately 2 × 107 PIMP existed in the lungs of 300 gram rats. The functionally heterogeneous mononuclear phagocytes exhibited phagocytic capacities ranging from avidly phagocytic (14.6 ± 9.8% ) through moderately active (33.9 ± 13.4%) to inactive. The lung microvasculature's large pool of inactive mononuclear phagocytes may provide a recruitable mechanism to allow significant increases in clearance of circulating particulates. A resident pool of activatable mononuclear phagocytes might explain previous clinical observations of increased particulate localization in the lung microvasculature of septic patients. Anat. Rec. 252:626–636, 1998. © 1998 Wiley-Liss, Inc.

Opsonic effect of globulins on phagocytosis of liposomes by bone marrow cells.

In recent years there has been a great surge in the development of particulate drug carriers for chemotherapy and diagnostic medicine. However, to realise the full potential of various drug carriers such as liposomes, it is necessary to understand how these particles are cleared from the circulation when injected intravenously, and what determines their recognition by the reticuloendothelial cells in the liver, spleen and bone marrow. In the circulation the drug carriers become coated with plasma components and this process is thought to determine their recognition by the reticuloendothelial cells. Liposomes coated in vifro with opsonins such as immunoglobulin, components of the complement system, fibronectin. C-reactive protein etc., when injected intravenously are cleared rapidly from the circulation (1). Recently we have demonstrated the presence of opsonins in serum which exhibit tissue specificity and described their properties which differentiate between 'liver-specific' and 'spleen-specific' opsonins responsible for the enhancement o f phagocytosis of liposomes by Kupffer cells and splenic macrophages respectively (2,3). However, so far there has been no clear indication to suggest the identity of the tissue-specific opsonin involved in phagocytosis of the injected liposomes. Bone marrow is one of the major organs of the reticuloendothelial system and plays a small but significant role in the clearance of foreign particulates including liposomes. In vifro serum is found to enhance the uptake of cholesterol-containing liposomes in the bone marrow cells. This opsonic activity of serum is destroyed when the serum is heated at 55°C for 30 min. This suggests that heat-labile complement may be involved in the phagocytosis of liposomes. However, when dialysed or EGTA-chelated serum is used, a complete loss of its opsonic activity occurs. Addition of the serum dialysate or divalent cations to the dialysed serum does not reinstall its lost opsonic activity (4). Thus these results shed doubt on the possibility of involvement of the complement and hence we searched for another heat-labile serum factor which may be responsible for enhancing phagocytosis of liposomes in these cells. Heat-labile pand y-globulin are known to enhance phagocytosis of certain strains of bacteria (1) and p-globulin is also known to enhance uptake of anionic liposomes into the perfused liver (5). Hence we examined the effect of various serum globulins on the uptake of neutral high cholesterol liposomes in the freshly prepared bone marrow Cells. The results in Table 1 show that y-globulin and immunoglobulin in the absence or presence of serum have little effect on the uptake of liposomes in the bone marrow cells, whereas p-globulin in the absence of serum stimulates the uptake of liposomes by 5-fold as compared to the control and it retains its opsonin activity in the presence of serum. Thus these results suggest that p-gloublin may be the heat-labile serum factor that enhances phagocytosis of liposomes in the bone marrow. Table 1