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PubMed2004

Properties of various phosphatidylcholines as emulsifiers or dispersing agents in microparticle preparations for drug carriers.

We investigated characteristics of various phosphatidylcholines (PCs) used as dispersing agents and emulsifiers. Six PCs with different lengths of acyl hydrocarbon chains and different degrees of unsaturated acyl hydrocarbon chains were selected to examine influences of a lipophillic part of phosphatidylcholines in emulsion and dispersion systems. Vesicles and oil-in-water emulsions were prepared by sonication under several ambient temperature conditions. Mean diameters of vesicles and oil droplets in emulsions were measured by a submicron particle sizer. In vesicles that are generated by hydration of the PCs and have a bilayer form, particle size was influenced by length and degree of unsaturation of acyl hydrocarbon chains of a PC. PCs with shorter acyl hydrocarbon chains or unsaturated bonds are considered more potent dispersing agents. Preparation temperature of the PC is also a factor affecting potency of dispersion. In O/W emulsions in which PCs were absorbed at water-oil interfaces and which have a single layer form or liquid-crystal layer form, particle size was also influenced by length and degree of unsaturation of acyl hydrocarbon chains of a PC. PCs with shorter and saturated acyl hydrocarbon chains are considered more potent emulsifiers. Unsaturation of acyl hydrocarbon chains weaken the ability of emulsification due to vulnerable double bonds. For stable emulsions, it is considered beneficial for PCs to form small oil droplets and lamellae liquid-crystal phase. From this perspective, saturated PCs with short hydrocarbon chains, i.e., DLPC and DMPC, may have advantages in preparing a stable emulsion not only by giving a smaller droplet size but also by forming lamellae liquid-crystal phase. When considering characteristics of PCs as emulsifiers, their characteristics as dispersing agents is also useful information.

Biocompatible Materials↗
PubMed2006

Preparation and physical characterization of a novel marine oil emulsion as a potential new formulation vehicle for lipid soluble drugs.

Emulsions often contain vegetable oils such as soybean oil. In this study, a 10% (w/w) of marine mammal oil emulsion was prepared. The effect of a group of emulsifying agents on the stability of the 10% of seal oil emulsion was examined. The emulsifying agents studied were hydrogenated castor oil coated with various polyoxyethylene derivatives. It was found that 2.5% of HCO-40 resulted in the most stable seal oil emulsion. The size of the emulsified droplets defined by their diameters was found to be around 240-270 nm. The initial zeta-potential and pH value of the emulsion were found to be around -27 mV and 3.5, respectively, which decreased over time, to about -31 mV and 2.4, respectively. This is believed to be a result of the hydrolysis of triacylglycerides into free fatty acids in the emulsion. The effect of various amounts of Crodasinic LS-30, a negatively charged surfactant, and Incroqal Behenyl TMS, a positively charged surfactant, on the emulsion was investigated. It was shown that Crodasinic LS-30 had very little effect on the particle size, zeta-potential and pH, while the effect of Incroquat Benhenyl TMS was found to be dependent upon the concentration of the surfactant used.

Animals↗
PubMed2006

Effect of various formulation parameters on the properties of polymeric nanoparticles prepared by multiple emulsion method.

This work evaluates and interprets underlying mechanisms behind various aspects related to preparation and physical characteristics of polymeric nanoparticles (NP). These were prepared from different biodegradable polymers according to a water-in-oil-in-water emulsion solvent evaporation method. Polymers used were poly(lactic-co-glycolic) acid (PLGA), poly (lactic acid) (PLA), (PLA-PEG-PLA) triblock and (PLA-PEG-PLA)n multi-block co-polymers. A model DNA, as an example of a hydrophilic drug, was encapsulated in the internal aqueous phase. The primary emulsion was prepared using a high shear turbine mixer. The secondary emulsion was prepared by high-pressure homogenization. Surface morphology and internal structure were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Influence of process variables on the physical properties of NP has been studied. Release of DNA was evaluated. In addition, changes occurring to NP porosity and surface area during degradation were followed. Nanoparticle size was ranging between 200-700 nm, according to the preparation conditions. Homogenizing pressure, concentration of the emulsifying agent used, polymer concentration and type and the concentration of a cryoprotectant had variable effects on NP size, surface area and porosity. Batches of NP where no emulsifying agent was added were obtained successfully. The release rate of the DNA from NP was mainly dependent on porosity, which varied significantly among used polymers. The preparation technique was efficient in encapsulating the model DNA and will be used for plasmid encapsulation in a future work.

Chemistry, Pharmaceutical↗
PubMed2001

Interaction between erythrocytes from three different animals and emulsions prepared with various lecithins and oils.

The hemolysis of various animal erythrocytes in emulsions prepared with various emulsifying agents (lecithins) and oils was examined. In the emulsions stabilized with different emulsifying agents, the degree of hemolysis increased in the order soybean lecithin<egg yolk lecithin<hydrogenated egg yolk lecithin<hydrogenated soybean lecithin. In the emulsions stabilized with phospholipids with different iodine values that describe the degree of unsaturation in the fatty acyl groups of phospholipids, the percentage hemolysis decreased with increasing iodine value. In addition, in emulsions prepared with various triglycerides as the oil phase the percentage hemolysis increased with increasing triglyceride acyl chain length. The percentage hemolysis of the different animal erythrocytes increased in the order sheep<rabbit<guinea pig according to phosphatidylcholine contents in erythrocyte membrane of each animal. These results suggested that hemolysis caused by the interaction between erythrocytes and emulsions was involved in phospholipid dispersal such as liposome-like vesicles in the water phase, and was dependent on the phosphatidylcholine contents in both the emulsions and the erythrocyte membrane. Moreover, sphingomyelin in the erythrocyte membrane was found to be an important component for stabilization of erythrocyte membranes against hemolysis induced by intravenous fat or lipid emulsions.

Journal Article↗
PubMed1983

Physicochemical transformation of milk components and release of foot-and-mouth disease virus.

Possible mechanisms for protective roles of milk components on foot-and-mouth disease virus present in the milk of infected cows were examined. Light scattering bands collected from Ficoll-sucrose gradient fractions of skim-milk contained membrane-limited structures but these were non-infectious for bovine kidney cells. Infectivity titres in buttermilk higher than those of the original cream or butter suggested association of virus with milk fat globules. Increased infectivity titres in skim-milk after treatment with SDS suggested release of virus particles from dissociated casein micelle subunits. Chelating agents, de-emulsifying agents and trypsin, which alter the structure of the individual milk components casein, lipid and milk fat globule membrane were without effect on infectivity titres.

Animals↗
PubMed2002

A study of identifying the emulsion type of surfactant: volume balance value.

A new method for identifying the emulsion type of surfactant is introduced--volume balance value, that is, the ratio of hydrophilic group and hydrophobic group volumes in surfactant. The radius used in the volume for the VB value comes from the Pauling radius based on quantum chemistry. The result shows that the surfactant is an o/w emulsifying agent and water-soluble when the VB is more than 1, and is a w/o emulsifying agent and oil-soluble when the VB is less than 1. The VB value possesses additivity.

Journal Article↗
PubMedDate not supplied

How do dermatological vehicles influence the horny layer?

Emulsifying agents in aqueous solution lead to dehydration of the horny layer of the epidermis and damage to the barrier. This is only partly true if emulsifying agents are constituents of emulsions. Water-in-oil (W/O) emulsions cause an improvement in the hydration of the horny layer and barrier function. In the case of an additional effect of wash solutions, a partial or complete abolition of the drying out and barrier-damaging effect of the wash solution results. Oil-in-water (O/W) emulsions without glycerol have no effect on the moisture of the horny layer or indeed increase it, but they lead to considerable damage to the barrier and irritation. In wash tests, they do not induce any protective effect. With micro-emulsions this is still more the case and, moreover, they can also lead to exsiccation. As a result of the addition of glycerol, the barrier-damaging effect can be abolished. Also in stress tests with wash solutions, the damage to the horny layer is reduced by glycerol-containing O/W emulsions. Whereas the penetration-promoting effect of O/W emulsions without glycerol is best, only W/O emulsions or glycerol-containing O/W emulsions are suitable for atopic dermatitis. A hydrating effect on the stratum corneum was also found in a propylene glycol ointment.

Emulsions↗
PubMed1991

[Releasing properties of water soluble drug in internal water phase of W/O/W multiple emulsions].

A stable water/liquid paraffin system water-in-oil-in-water (W/O/W) multiple emulsion was prepared by the two-step procedure of emulsification using a variety of nonionic emulsifying agents, such as Span 80 and Tween 20. After comparison of the releasing properties of such water soluble drugs as cefadroxil, cephradine, 4-aminoantipyrine and antipyrine which were entrapped separately in the inner aqueous phase of the W/O/W multiple emulsion, a large difference was observed. It was ascertained that the difference in these releasing properties was due to no physical rupture by the microscopic observation and the results of the release test of W/O/W multiple emulsion with two kinds of drugs entrapped simultaneously in an inner aqueous phase. This reason was presumed to be dependent on permeation in the oily phase of the drug itself. It was proved that the differences of releasing properties tended to depend on the molecular weight and were closely related to the drug concentration of outer aqueous phase of W/O/W multiple emulsion containing the drug in both aqueous phases prepared as an experimental model. Therefore, two possible mechanisms for the releasing of drugs in W/O/W multiple emulsion may be interpreted as follows: the first is that the mixed and inversed micelles formed by Span 80 and Tween 20 agents in the oily phase act as a carrier of drugs, and the second is that drug molecules diffuse through small pore existing in very thin lamella of the emulsifying agents partially formed in the oil layer owing to the fluctuation of the thickness.

Ampyrone↗
PubMed1989

Interaction between erythrocytes from various animals and emulsions stabilized with various lecithins.

The degree of hemolysis caused by the interaction between erythrocytes from various animals and emulsions stabilized with various lecithins was evaluated as a measure of the safety of emulsions for drug carriers. The stability of the emulsions was estimated using the gradient of the slope derived from the direct linear correlation between the percentage hemolysis and the phosphatidylcholine (PC) content of the erythrocyte membrane. When members of the egg lecithin (EPC) series were used as emulsifiers of emulsions, the percentage hemolysis increased as the PC content of the erythrocyte membrane increased and as the sphingomyelin (SM) content of the erythrocyte membrane decreased. Lysolecithin, a contaminant present in the emulsifying agent of emulsions, did not have any significant influence on the hemolysis of erythrocytes. These experimental findings show that the hemolysis caused by interaction between emulsions and erythrocytes was dependent on the PC content of both the emulsifying agent used and the erythrocyte membrane, and that the SM present in the erythrocyte membrane was an essential component for the stability of erythrocytes against emulsion-induced hemolysis.

Animals↗
PubMedDate not supplied

Some emulsifying and suspending properties of the mucilage extracted from kernels of Irvingia gabonensis.

The mucilage extracted from the kernels of Irvingia gabonensis was evaluated for use as suspending and emulsifying agent. The rheological behaviour of the mucilage was studied and compared to that of tragacanth. As a suspending agent, Irvingia mucilage was compared to tragacanth at various concentrations (0.5, 1.0, 1.5 and 2.0% w/v) in the formulation of sulphanilamide suspensions. At all concentrations the formulated suspensions with Irvingia mucilage gave higher Hu (final sedimentation height) and F (sedimentation volume) values. As an emulsifying agent, the properties of Irvingia mucilage was compared to tragacanth and acacia gum. The emulsions prepared with 0.6, 1.0, and 1.5% tragacanth and Irvingia 'cracked' within six days while that with 12.5% w/v acacia started showing signs of creaming at the tenth day. The emulsion prepared with 2.0% w/v Irvingia mucilage was however stable throughout the six weeks of study. The results indicate that Irvingia mucilage performed better than acacia and tragacanth even at lower concentrations in the formulation of emulsions and suspensions.

Adhesives↗
PubMed1989

[Chemotherapy combined with Lipiodol. In vitro study of the kinetics of release of adriamycin].

Intra-arterial injection of lipiodol-adriamycin mixtures are commonly used in the treatment of hepatic tumors based on the progressive release of adriamycin. This study was undertaken to assess, in vitro, the influence of mixture formulations on the adriamycin release pattern. Eight mixtures containing 10 mg of adriamycin were tested. Adriamycin was tested in solution (mixture A) in suspension (mixture B), or in emulsions with Hexabrix 320 (mixtures C to F). Ratios between Hexabrix and lipiodol volumes were 2/1, 1/1, 1/2, and 1/4 for emulsions C, D, E, and F, respectively. Emulsions G and H corresponded to emulsions E and F, with Arlacel A as emulsifying agent. All mixtures were prepared in triplicate and added with water. Samples of 200 microliters were taken from the aqueous phase after 10, 20, 30 min, 1, 2, 4, 8, 24, 48, 72, and 120 h for adriamycin dosage. Lipiodol-adriamycin mixture formulation significantly influenced the release pattern of adriamycin. Three formulations (suspension, emulsions 2/1 and 1/4) induced the most progressive release of adriamycin from lipiodol. This release was dramatically retarded by the addition of an emulsifying agent.

Delayed-Action Preparations↗
PubMed1976

Contact sensitivity to emulsifiers.

Common emulsifiers were tested in over 1,200 patients with eczema. Triethanolamine stearate tested at 5% in petrolatum caused irritant reactions in 9.5% of the patients. On the other hand, non-ionic emulsifying agents tested at 10-20% produced irritation in only a few cases. Allergic reactions were found in 2.1% of those tested. Lanette, sorbitan sesquioleate, the Spans, polyoxyethylene oxypropylene stearate, polyoxyethylene sorbitol lanolin derivative, and triethanolamine stearate each elicited allergic reactions in 0.3-0.7% of the cases. The Tweens caused an allergy in only two cases, but glycerol monostearate caused no reaction at all. Five out of six patients sensitive to sorbitan sesquioleate reacted positively to the Spans as well. The patients allergic to one or more emulsifiers were also sensitive to several other substances included in our routine test series with the exception of four patients who reacted only to the emulsifying agents.

Dermatitis, Contact↗
PubMed2004

Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate.

The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed in a safety assessment completed in 2000. Additional safety test data pertaining to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served as the basis for this amended report. Glyceryl monoesters are used mostly as skin-conditioning agents--emollients and/or surfactant--emulsifying agents in cosmetics. The following 20 glyceryl monoesters are currently reported to be used in cosmetics: Glyceryl Laurate, Glyceryl Alginate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Cocoate, Glyceryl Erucate, Glyceryl Hydroxystearate, Glyceryl Isostearate, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Myristate, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Stearate/Acetate, and Glyceryl Undecylenate. Concentration of use data received from the cosmetics industry in 1999 indicate that Glyceryl Monoesters are used at concentrations up to 12% in cosmetic products. Glyceryl Monoesters are not pure monoesters, but are mostly mixtures with mono-, di-, and tri-esters. The purity of commercial and conventional Monoglyceride (Glyceryl Monoester) is a minimum of 90%. Glyceryl Monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides. Glyceryl Laurate enhanced the penetration of drugs through cadaverous skin and hairless rat skin in vitro and has been described as having a wide spectrum of antimicrobial activity. A low-grade irritant response was observed following inhalation of an aerosol containing 10% Glyceryl Laurate by test animals. Glyceryl monoesters have little acute or short-term toxicity in animals, and no toxicity was noted following chronic administration of a mixture consisting mostly of glyceryl di- and mono- esters. Glyceryl Laurate did have strong hemolytic activity in an in vitro assay using sheep erythrocytes. Glyceryl Laurate, Glyceryl Isostearate, or Glyceryl Citrate/Lactate/Linoleate/Oleate were not classified as ocular irritants in rabbits. Undiluted glyceryl monoesters may produce minor skin irritation, especially in abraded skin, but in general these ingredients are not irritating at concentrations used in cosmetics. Glyceryl monoesters are not sensitizers, except that Glyceryl Rosinate and Hydrogenated Glyceryl Rosinate may contain residual rosin, which can cause allergic reactions. These ingredients are not photosensitizers. Glyceryl Citrate/Lactate/Linoleate/Oleate was not mutagenic in the Ames test system. Glyceryl Laurate exhibited antitumor activity and Glyceryl Stearate was negative in a tumor promotion assay. At concentrations higher than used in cosmetics, Glyceryl Laurate did cause moderate erythema in human repeat-insult patch test (RIPT) studies, but the other glyceryl monoesters tested failed to produce any significant positive reactions. Glyceryl Rosinate was irritating to animal skin at 50%, but did not produce sensitization in clinical tests at concentrations up to 10% and covered with semioccluded patches. There is reported use of Glyceryl Rosinate at 12%in mascara, which is somewhat higher than the concentration in the clinical testing. It was reasoned that the available data do support the safety of this use because there would be minimal contact with the skin and no occlusion. The safety of Arachidonic Acid was not documented and substantiated for cosmetic product use in an earlier safety assessment and those same safety questions apply to Glyceryl Arachidonate. Based on these data, the Cosmetic Ingredient Review (CIR) Expert Panel found that these glyceryl monoesters are safe as cosmetic ingredients in the present practices of use and concentration: except that the available data are insufficient to support the safety of Glyceryl Arachidonate. Additional data needed to support the safety of Glyceryl Arachidonate include (1) dermal absorption data; and, based on the results of the absorption studies, there may be a need for (2) immunomodulatory data; (3) carcinogenicity and photocarcinogenicity data; and (4) human irritation, sensitization, and photosensitization data.

Animals↗
PubMed2004

A novel convenient procedure for extractive work-up of whole-cell biotransformations using de-emulsifying hydrolases.

Extractive work-up of whole-cell biotransformations generally suffers from the formation of stable gels and slimes upon addition of the organic solvent to the cell suspension and the cell-free solution, respectively. This problem has been overcome by enzymatic lysis of emulsifying agents present in the medium through addition of hydrolases. Of these agents, proteases have exhibited the most powerful de-emulsifying activity. Enzyme treatment of cell-free culture media of Saccharomyces cerevisiae with pronase E drastically reduced phase separation time (t(p)) from 1 week to 30 min without significantly affecting product integrity. Yeast cell suspensions were de-emulsified best with protease N-01, where phase separation was complete after 1 h. As was exemplified with cell-free culture media of Lactobacillus kefir, wherein addition of pronase E or protease N-01 reduced t(p) from 1 week to 2 h each, this practical, ready-to-use method is appropriate for both fungal and bacterial biocatalysts.

Bacterial Proteins↗
PubMed1976

Allergy to ingredients of vehicles.

Common ingredients of vehicles such as perfumes, antibacterial agents, emulsifiers and other surface active agents, propylene glycol, lanolin and wool alcohols were tested in eczema patients over a three-year period. Perfume allergy was detected in 3.6% of the cases, sensitivity to thiomersal in 2%, to sorbic acid in 0.8%, to parabens in only 0.3%, and to wool alcohols in 1.2%. Reactions to emulsifiers were seen over 1% of those tested.

Adult↗
PubMed2001

Final report on the safety assessment of Lecithin and Hydrogenated Lecithin.

Lecithin is a naturally occurring mixture of the diglycerides of stearic, palmitic, and oleic acids, linked to the choline ester of phosphoric acid, commonly called phosphatidylcholine. Hydrogenated Lecithin is the product of controlled hydrogenation of Lecithin. Bilayers of these phospholipids in water may form liposomes, a spherical structure in which the acyl chains are inside and not exposed to the aqueous phase. Lecithin and Hydrogenated Lecithin are used in a large number of cosmetic formulations as skin conditioning agents-miscellaneous and as surfactant-emulsifying agents. Hydrogenated Lecithin is also used as a suspending agent-nonsurfactant. Historical data on concentration of use of Lecithin reveals that 0.1% to 1.0% is the concentration range most frequently seen, with concentrations up to 50% reported for two moisturizing products. A solution of 65% Lecithin is currently reported to be used at concentrations up to 3% in cosmetics. Nonocclusive application of Lecithin-containing liposomes to murine skin resulted in 30% penetration to the subdermis. In piglet skin, the same application resulted in 99% accumulating in the stratum corneum. In general, liposomes are considered effective in capturing other compounds inside their spherical structure and delivering any such captured compound through the skin barrier. As a result, caution should be exhibited in formulating cosmetic products that contain these ingredients in combination with other ingredients whose safety is based on their lack of absorption or where dermal absorption is a concern. Lecithin is virtually nontoxic in acute oral studies, short-term oral studies, and subchronic dermal studies in animals. Lecithin is not a reproductive toxicant, nor is it mutagenic in several assays. In an oral carcinogenicity study, brain neoplasms were found in mice exposed to Lecithin. In a subcutaneous carcinogenicity study, no neoplasms were found in mice and rats exposed to Lecithin. Adverse reactions to Lecithin in a metered-dose inhaler have been reported. Lecithin and Hydrogenated Lecithin were generally nonirritating and nonsensitizing in animal and human skin. Based on the available data, Lecithin and Hydrogenated Lecithin are safe as used in rinse-off cosmetic products; they may be safely used in leave-on products at concentrations up to 15%, the highest concentration tested in clinical irritation and sensitization studies; but the safety of use could not be substantiated in cosmetic products likely to be inhaled. Because of the possibility of formation of nitrosamines, these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.

Administration, Inhalation↗
PubMed2003

Biosynthesis and assembly of Group 1 capsular polysaccharides in Escherichia coli and related extracellular polysaccharides in other bacteria.

Extracellular and capsular polysaccharides (EPSs and CPSs) are produced by a wide range of bacteria, including important pathogens of humans, livestock, and plants. These polymers are major surface antigens and serve a variety of roles in virulence, depending on the biology of the producing organism. In addition to their importance in disease, some EPSs also have industrial applications as gelling and emulsifying agents. An understanding of the processes involved in the synthesis and regulation of CPSs and EPSs therefore potentially contributes to an understanding of the disease state, surface expression of protective antigens, and modulation of polymer structure to give defined physical properties. Escherichia coli has provided important model systems for EPS and CPS biosynthesis. Here we describe current knowledge concerning assembly of the Group 1 CPSs of E. coli and the conservation of similar mechanisms in other bacteria.

Antigens, Bacterial↗
PubMed2005

Nasal administration of heparin-loaded microspheres based on poly(lactic acid).

In this study, heparin-loaded microspheres having smooth surface and small particle size were designed in order to provide the absorption of heparin through nasal mucosa. For this purpose, microspheres at different polymer/drug ratios (1:10, 1:2.5 and 1:1) and at different concentrations of polyvinyl alcohol, emulsifying agent (1.5% and 2.5% w/v) were prepared by solvent evaporation method with poly(lactic acid). The microspheres were for evaluated shape and surface properties, particle size, production yield, encapsulation efficiency and in vitro drug release. Based on the in vitro data, selected microspheres were applied by nasal route to Wistar albino rats. According to in vivo studies, heparin-loaded microspheres may be used by nasal route as an alternative to parenteral route.

Administration, Intranasal↗