Effect of various formulation variables on the encapsulation and stability of dibucaine base in multilamellar vesicles

Formulation of local anesthetics in liposomal topical drug delivery system could provide a sustained and localized anesthesia. The aim of this study was to develop a liposomal dibucaine base (DB) local anesthetic delivery system. DB-loaded multilamellar vesicles (MLVs) were prepared through varying lipid composition, induced charge and pH of the hydration medium. Liposomes were characterized for morphology, size, entrapment efficiency (EE), in vitro drug release and stability including leakage stability. The percentage of drug entrapped in liposomes was found to be hydration medium pH dependent and charge dependent and more pronounced for negatively charged liposomes prepared using hydration medium of pH 9. In vitro release studies of liposomes have shown a sustained release of entrapped dibucaine compared to control solution. Results revealed that adjusting the various formulation variables of dibucaine base MLVs could yield stable and effective topical liposomal local anesthetic formulations.     

Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation

Silymarin is a natural lipotropic agent of low bioavailability from oral products. The aim of our study is to prepare buccal liposomal delivery system of silymarin with higher bioavailability. The effect of lecithin:cholesterol molar ratio on the percentage drug encapsulated was investigated. The influence of fluctuating the amount of added drug was also determined. The effect of additives such as positive charge inducer, negative charge inducer and surfactants was studied using two different 2(3) full factorial designs. Furthermore, additives used to optimize liposomal product were also investigated for their optimal concentrations, release properties and in vitro permeation and absorption through chicken cheek pouch. Optimal liposomal encapsulation efficiency was found at 7:4 lecithin to cholesterol molar ratio. A decrease in entrapment efficiency with increasing cholesterol content was observed. Tween 20 or Tween 80 beyond 0.5 molar ratio decreased the entrapment efficiency. Positively charged liposomes showed superior entrapment efficiency over neutral and negatively charged liposomes. Release studies as well as permeation and absorption studies showed that hybrid liposomes prepared according to formula 3 containing lecithin, cholesterol, stearyl amine and Tween 20 in 9:1:1:0.5 molar ratio, respectively, gave the best drug absorption and permeation. It showed steady state permeation through chicken cheek pouch for 6h. This is expected to improve the bioavailability of silymarin in the developed liposomal buccal delivery system, as the results show an increase in drug penetration compared to free drug powder.     

Development and characterization of dutasteride bearing liposomal systems for topical use

Dutasteride loaded liposomal system were developed for topical application in order to avoid the side effects associated with the oral administration of the drug. Drug-loaded multilamellar liposomes were prepared using thin-film hydration method followed by sonication and optimized with respect to entrapment efficiency, drug payload, size and lamellarity. The vesicular systems consisting of egg phosphatidylcholine (100 mg), cholesterol (50 mg), and dutasteride (5 mg) showed highest drug entrapment efficiency (94.6%) and drug payload (31.5 μg/mg of total lipids). Mean vesicle size of these liposomes was noted to be 1.82 ± 0.15 μm. Significantly higher skin permeation of dutasteride through excised abdominal mouse skin was achieved via the developed liposomal formulations as compared to hydro-alcoholic solution and conventional gels. The formulation exhibited about seven fold higher deposition of drug in skin. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 10 weeks with negligible drug leakage or vesicle size alteration. Results of the current studies exhibited improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.     

Free versus liposome-encapsulated lignocaine hydrochloride topical applications.

The influence of encapsulating lignocaine hydrochloride, in a liposomal delivery system on its release from a topical formulation was studied. Liposomes were prepared from a mixture of L-alpha-dipalmitoylphosphatidyl choline (DPPC) and cholesterol in different molar ratios with or without charge inducing agents. The swelling time affording maximum entrapment was tested from 0-48 h at 53 degrees C. The percentage of drug entrapped in liposomes was found to be charge dependent and more pronounced for negatively charged liposomes. The amount of drug entrapped increased by increasing the ratio of cholesterol. The selected formulations were evaluated in vivo using the pin prick method. The results revealed localized and prolonged activity of lignocaine contained in liposomes when compared with an equivalent conventional topical application.     

Release stability of 5-fluorouracil liposomal concentrates, gels and lyophilized powder

Possible leakage of 5-fluorouracil from stable plurilamellar vesicles was monitored during storage of the liposomal concentrates, gels and lyophilized powders. Changes in release profile of dibucaine were taken as indicator of instability. Release profiles were obtained using the dialysis technique for a freshly prepared liposomal concentrate, gel or reconstituted lyophilized powder (zero time) and storage for one, two and four weeks in well closed tubes at 4 degrees C for the liposomal concentrate or gel and at 25 degrees C for liposomal lyophilized powder. Aiming at increasing stability of 5-fluorouracil liposomal dispersion, freshly prepared liposomal concentrates were directly incorporated in hydroxypropyl methylcellulose gel. Stability release profiles of liposomal gels and concentrates indicated a significant increase in stability of liposomal formulations. Also, lyophilization increases the shelf life of liposomes by preserving it in a dry form as a lyophilized cake to be reconstituted immediately prior to administration or direct incorporation into a final dosage form. Release and physico-chemical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison to concentrate and gel forms. It could be concluded that lyophilization of liposomes loaded with a water-soluble drug such as 5-fluorouracil could significantly increase the stability of the liposomal vesicles and decrease leakage from it.     

Formulation and characterization of azidothymidine-loaded liposomes

Entrapment efficiency (EE%) and in vitro stability of azidothymidine (AZT)-loaded hand-shaken multilamellar vesicles (MLVs), freeze and thaw vesicles (FATMLVs), and reverse phase evaporation vesicles (REVs) were compared. AZT entrapment in FATMLVs was further studied by varying initial lipid concentrations, drug concentration, and lipid composition. The results suggest that AZT entrapment is dependent on the aqueous volume entrapped within liposomes, and the interaction between the drug and liposomal bilayer may not be significant. Increasing the lipid concentration increases the liposomal entrapment of AZT but the encapsulation yield decreases above a lipid concentration of 30 μmol/mL. No significant difference was observed in EE% when the AZT concentration was varied from 5 to 20 mg/mL. The entrapment efficiency was highest (43.2%) for DSPC/CHOL/PS (molar ratio 6:3:3) vesicles but DSPC/CHOL/PS liposome formulations in a molar ratio of 4:3:3 or 4:5:1 and DSPC/CHOL/SA liposome formulations in a molar ratio of 4:5:1 were found to be more stable in vitro. In vitro drug release from liposomes was dependent on bilayer composition and the method of preparation.     

Caffeine-loaded niosomes: characterization and in vitro release studies

We prepared different neutral and positively charged niosomal formulations containing sorbitan esters for entrapment of caffeine. Drug entrapment reduced following the incorporation of positively charged molecule. Furthermore, the span 60-containing niosomes showed the highest drug encapsulation efficiency due to solid-state nature of this surfactant's bilayers. There was a regular relationship between lipophilicity (HLB values) of surfactants and mean particle sizes; increasing the HLB value resulted in larger niosomes. By means of diffusion experiments with Franz diffusion cells, the effects of different vesicular components and that of the positive charge on the release of caffeine from various vesicle formulations were studied. Obtained results indicate that a combined erosion-diffusion mechanism regulates the permeation of caffeine through cellulose acetate membranes. High encapsulation efficiency, appropriate size distribution, and good vesicular stability, especially in solid state niosomes, make this type of vesicular systems a good alternative to liposomes for topical delivery of caffeine.     

The extended ocular hypotensive effect of positive liposomal cholesterol bound timolol maleate in glaucomatous rabbits

Increased intraocular pressure (IOP) is a significant risk factor for the development of glaucoma. Timolol maleate is a beta-adrenergic receptor blocking agent and it is used for the treatment of glaucoma in order to reduce the elevated IOP that is characteristic of this eye disease. Systemic toxicity from topical timolol occurs more frequently than local toxicity and can affect the pulmonary, cardiac and central nervous systems. The objective of the present study, therefore, was to formulate multilamellar vesicles (MLVs) liposomal preparations of timolol maleate using their advantage of being less toxic compared with non-liposome-based drugs to be applied topically and to evaluate the in vivo performance of the prepared liposomes to extend the time of reduced IOP of glaucomatous rabbit's eye measured using a standard Shiotz tonometer. The encapsulation efficiency of MLVs was measured using a spectrophotometric technique. Differential scanning calorimetry (DSC) was used to monitor the effects of timolol maleate in the absence and presence of cholesterol on liposome thermal behaviour. Positively charged MLVs of timolol in the presence of a lower amount of cholesterol (DPPC(7):Chol(2):Timolol(2):SA(1) molar ratio) were found to be superior compared with other formulations in extending the ocular hypotensive effect approximately for 1 week (160 h) which encourages its physiological effectiveness. The increase of the cholesterol molar ratio in the prepared liposomal formulations serves to decrease the permeability of the lipid bilayer that is manifested by a low rate of drug release, an increased percentage of entrapment efficiency and a consequently lower bioavailability.     

Improved Permeability of Acyclovir: Optimization of Mucoadhesive Liposomes Using the Phospholipid Vesicle-Based Permeation Assay

The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations’ mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration.     

Lyophilization of cholesterol-free PEGylated liposomes and its impact on drug loading by passive equilibration

The obstacles in translating liposome formulations into marketable products could be attributed to their physical instabilities upon long-term storage as aqueous dispersions. Lyophilization is the most commonly used technique to improve physical stability of liposomes. The development of stable, lyophilized liposomes is focused primarily on the cholesterol-containing liposomes or pure phosphatidylcholine-based liposomes, with minimal studies on cholesterol-free, pegylated (CF-PEG) liposomes which have emerged as an important class of liposome drug carriers. Hence, it is our interest to investigate the effect of lyophilization on CF-PEG liposomes, and specifically, on drug loading via the passive equilibration method. Three different sugar cryoprotectants were used at two different sugar-to-lipid molar ratios (S/L). Our results demonstrated that CF-PEG liposomes lyophilized with sucrose at S/L=5:1 yielded the best cryoprotective effect, as characterized by size, polydispersity indices, and microscopic examination upon liposome reconstitution. The lyophilized liposomes had low water content of 2.59 ± 0.18%. Of note, lyophilized CF-PEG liposomes exhibited two-fold increase in drug content when carboplatin was loaded via the passive equilibration method, and the in vitro drug release profile of these liposomes were not different from that of the non-lyophilized counterparts. Taken together, we envisioned that a stable, lyophilized empty CF-PEG liposome system could be coupled to hydrophilic drug loading via the passive equilibration method to produce a liposomal drug kit product.     

Vesicular aceclofenac systems: A comparative study between liposomes and niosomes

Vesicular delivery systems have been reported to serve as local depot for sustained drug release. Aceclofenac multilamellar liposomes and niosomes were prepared and a comparative study was done between them through evaluation of entrapment efficiency, particle size, shape, differential scanning calorimetry and in vitro drug release. A stability study was carried out by investigating the leakage of aceclofenac and the change in the vesicles particle size when stored at (2–8°C) for 3 months. The anti-inflammatory effect of aceclofenac vesicles was assessed by the rat paw oedema technique. Results showed that the entrapment efficiency and the in vitro release of aceclofenac from the vesicles can be manipulated by varying the cholesterol content, the type of surfactant as well as the type of charge. Niosomes showed better stability than liposomes. Both vesicular systems showed significant sustained anti-inflammatory activity compared to the marketed product, with niosomes being superior to liposomes as manifested by both oedema rate and inhibition rate percentages suggesting their effectiveness as topical anti-inflammatory delivery systems.     

Vesicular aceclofenac systems: a comparative study between liposomes and niosomes

Vesicular delivery systems have been reported to serve as local depot for sustained drug release. Aceclofenac multilamellar liposomes and niosomes were prepared and a comparative study was done between them through evaluation of entrapment efficiency, particle size, shape, differential scanning calorimetry and in vitro drug release. A stability study was carried out by investigating the leakage of aceclofenac and the change in the vesicles particle size when stored at (2-8 degrees C) for 3 months. The anti-inflammatory effect of aceclofenac vesicles was assessed by the rat paw oedema technique. Results showed that the entrapment efficiency and the in vitro release of aceclofenac from the vesicles can be manipulated by varying the cholesterol content, the type of surfactant as well as the type of charge. Niosomes showed better stability than liposomes. Both vesicular systems showed significant sustained anti-inflammatory activity compared to the marketed product, with niosomes being superior to liposomes as manifested by both oedema rate and inhibition rate percentages suggesting their effectiveness as topical anti-inflammatory delivery systems.     

Caffeine-Loaded Niosomes: Characterization and in Vitro Release Studies

We prepared different neutral and positively charged niosomal formulations containing sorbitan esters for entrapment of caffeine. Drug entrapment reduced following the incorporation of positively charged molecule. Furthermore, the span 60-containing niosomes showed the highest drug encapsulation efficiency due to solid-state nature of this surfactant's bilayers. There was a regular relationship between lipophilicity (HLB values) of surfactants and mean particle sizes; increasing the HLB value resulted in larger niosomes. By means of diffusion experiments with Franz diffusion cells, the effects of different vesicular components and that of the positive charge on the release of caffeine from various vesicle formulations were studied. Obtained results indicate that a combined erosion-diffusion mechanism regulates the permeation of caffeine through cellulose acetate membranes. High encapsulation efficiency, appropriate size distribution, and good vesicular stability, especially in solid state niosomes, make this type of vesicular systems a good alternative to liposomes for topical delivery of caffeine.     

Design and Evaluation of Liposomal Formulation of Pilocarpine Nitrate

Prolonged release drug delivery system of pilocarpine nitrate was made by optimizing thin layer film hydration method. Egg phosphatidylcholine and cholesterol were used to make multilamellar vesicles. Effects of charges over the vesicles were studied by incorporating dicetylphosphate and stearylamine. Various factors, which may affect the size, shape, encapsulation efficiency and release rate, were studied. Liposomes in the size range 0.2 to 1 µm were obtained by optimizing the process. Encapsulation efficiency of neutral, positive and negatively charged liposomes were found to be 32.5, 35.4 and 34.2 percent, respectively. In vitro drug release rate was studied on specially designed model. Biological response in terms of reduction in intraocular pressure was observed on rabbit eyes. Pilocarpine nitrate liposomes were lyophilized and stability studies were conducted.     

Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate

Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.     

Release profile of lidocaine HCl from topical liposomal gel formulation

Liposomal hydrogel formulations of lidocaine HCl, suitable for topical application, have been prepared and drug release properties in vitro have been evaluated. Liposomes composed of Soya lechitin and cholesterol, with lidocaine HCl, entrapped in the inner water compartment, were prepared by simple hydration method. Topical liposomal gel formulations were prepared by incorporation of liposomes into a structured vehicle (hydrogels of Carbopol 940 in concentration of 1.5, 1.75 and 2%). High percentage of encapsulated drug in liposomes has been obtained (over 70%). Liposomal gel formulations provided prolonged drug release rate. The concentration of gelling agent in a range 1.5-2.0% affected the release rate slightly. In vitro release data showed that release kinetic can be described as diffusion-controlled, while liposomes act as reservoir systems for continuous delivery of drug. Proposed formulations provided stable percentage of entrapped drug and drug release within an examination period of 3 weeks.     

Biodistribution of liposome-entrapped human gamma-globulin

The present study was aimed at the preparation and performance evaluation of Intacglobin-loaded liposomes for selective drug presentation to the lungs. Egg phosphatidylcholine- and cholesterol-based liposomes (1:1 and 1:0.25 mol/mol) were prepared by a dehydration-rehydration procedure. A tissue distribution study after single intranasal administration of 0.5 microCi 125I-Intacglobin-loaded liposomes was conducted in Balb/c mice. The efficiencies of drug entrapment (30%) and the average diameters did not differ significantly between the two liposome formulations. However, liposomes composed of an increased cholesterol amount showed a lower in vitro drug release rate. The airway penetration efficiency of the liposomal formulation was determined by the cumulative percentage of the dose reaching the lungs (AUC) and its sojourn time therein, and were 1.7- and 2.2-times higher compared with the plain 125I- Intacglobin solution-based formulation, respectively. A significantly greater (p<0.001) drug localization index after 24 h was found at the lungs in comparison with the other tissues (p<0.01), although similar values were detected between groups following administration of either liposomes or control solutions, despite the formulations attributes. In conclusion, it is suggested that longer Intacglobin exposure at the pulmonary region is observed after administration of the liposomal formulation. The results open future perspectives in assessing local passive immunization for the treatment of respiratory infectious diseases.     

Preliminary investigation of the nasal delivery of liposomal leuprorelin acetate for contraception in rats

The purpose of the study was to investigate the nasal route as a non-invasive alternative for delivery of leuprorelin acetate (leuprolide acetate, LEU) and to achieve an effective concentration of leuprorelin acetate in blood after nasal administration for contraception in rats. The plain drug solution, physical mixture (plain drug along with constituents of liposomes), or drug encapsulated in either neutral or charged liposomes containing 5 microg leuprorelin acetate were administered to rats through the nasal route. The plain drug solution was administered subcutaneously (s.c.). Simultaneous evaluation was performed on the influence of a mucoadhesive agent (chitosan) on nasal absorption of the plain drug and the liposome-encapsulated drug. Blood samples were taken at regular time intervals and subjected to luteinising hormone (LH) analysis using a specific immunoassay kit. The plasma luteinising hormone concentration vs time data of nasal and subcutaneous treatments were plotted and compared with that of subcutaneous administration. Relative percentage of bioavailability (F) for nasal treatments was calculated from plasma concentration vs time plots. Sperm count and fertility performance studies were carried out for selected formulations in rats. Neutral liposomes (LLEU) and negatively-charged liposomes (LLEUn) showed higher relative percentage of bioavailability (F 27.83 and 21.30%, respectively) as compared with the plain drug and the physical mixture (F 10.89 and 10.96%, respectively) after nasal administration. Hence, work on neutral liposomes was continued. F was further improved after incorporation of chitosan i.e. 10.89 to 49.13% for plain leuprorelin acetate and 27.83 to 88.90% for liposomal leuprorelin acetate formulations. Liposomal chitosan formulation administered nasally and leuprorelin acetate solution subcutaneously achieved complete azoospermia. No implantation sites were observed after the mating of female rats with treated males. It was observed that in the treated female rats, the estrous cycles ceased with the same formulations from the first treatment cycle. The findings of these investigations demonstrated that the bioavailability of the nasally-administered liposomal leuprorelin acetate with chitosan formulation was comparable with that of the subcutaneously administered drug. Complete contraception was obtained in male and female rats that had been treated with either the nasally administered liposomal leuprorelin acetate with chitosan or the subcutaneously administered drug.     

The effect of ileal brake activators on the oral bioavailability of atenolol in man

The aims of this study were to develop novel liposome formulations for tranexamic acid (TA) from various lipid compositions [neutral (hydrogenated soya phosphatidylcholine and cholesterol), positive (stearylamine) or negative (dicetyl phosphate) charged lipid], and to investigate the effects of concentrations of TA (5 and 10% in DI water) and charges on the physicochemical properties of liposomes. Liposomes were prepared by chloroform film method with sonication. The physical (appearance, pH, size, morphology) and chemical (drug encapsulation efficiency, transition temperature, enthalpy of transition) properties of liposomes were characterized. The TA contents were determined spectrophotometrically at 415 nm, following derivatization with 2,4,6-trinitrobenzosulfonic acid. The charged liposomes demonstrated better physical stability than the neutral liposomes. The percentages of TA entrapped in all liposome formulations varied between 13.2 and 15.6%, and were independent of TA concentrations and charges of liposomes. Charges affected the physical stability, pH and size of liposomes. The particle sizes of negative blank and positive liposomes (with and without the entrapped drug) were approximately 10 times larger than the negative liposome with the entrapped TA. The multilamellar 7:2:1 molar ratio of hydrogenated soy phosphatidylcholine/cholesterol/dicetyl phosphate entrapped with 10% TA liposome (10%TA,-) was selected for further release study, due to its high physical stability, small particle size and relatively high drug encapsulation efficiency.     

Design of liposomal aerosols for improved delivery of rifampicin to alveolar macrophages

The present study was aimed at preparation, characterization, and performance evaluation of rifampicin-loaded aerosolized liposomes for their selective presentation to alveolar macrophages, that being the most dense site of tuberculosis infection. Egg phosphatidylcholine (PC)- and cholesterol (Chol)-based liposomes were modified by imparting negative charge (using dicetylphosphate, DCP) or by coating them with alveolar macrophage-specific ligands (maleylated bovine serum albumin, MBSA; and O-steroyl amylopectin, O-SAP). The prepared formulations were characterized in vitro for vesicle morphology, mean vesicle size, and percent drug entrapment. Pressurized packed systems based on preformed liposomal formulations in chlorofluorocarbon aerosol propellants were prepared. In vitro airway penetration efficiency of the liposomal aerosols was determined by percent dose reaching the base of the lung, it was recorded 1.5-1.8 times higher as compared to plain drug solution-based aerosol. Percent viability of Mycobacterium smegmatis inside macrophages (in vitro) after administration of drug (in vivo) was in the range of 7-11% in the case of ligand-anchored liposomal aerosols, while it was recorded to be 45.7 and 31.6% in case of plain drug and plain neutral liposomal aerosol (based on PC:Chol)-treated macrophages. Results suggest the preferential accumulation of MBSA- and O-SAP-coated formulations in the lung macrophages, which was further reflected in the periodically monitored in vivo tissue distribution studies. Higher lung drug concentration was recorded in case of ligand-anchored liposomal aerosols and negatively charged liposomal aerosols (based on PC:Chol:DCP) as compared to plain drug and plain liposome-based aerosols. The drug was estimated in the lung in high concentration even after 24h. The drug localization index calculated after 6h was nearly 1.4- and 3.5-fold, respectively, for both ligand-appended liposome-based systems as compared to negatively charged and plain neutral liposome-based aerosolized systems. These results suggest that the ligand-anchored liposomal aerosols are not only effective in rapid attainment of high-drug concentration in lung with high population of alveolar macrophages but also maintain the same over prolonged period of time. The significance of targeting potential of the developed systems was established.