Specific Drug Delivery System Research Articles

Design and development of mixed film of pectin: ethyl cellulose for colon specific drug delivery of sennosides and triphala.

The present study was aimed at developing colon specific drug delivery system for sennosides and Triphala. These drugs are reputed Ayurvedic medicines for constipation in India. The proposed device explored the application of pectin and ethyl cellulose as a mixed film for colon specific delivery. This mixed film was prepared using non-aqueous solvents like acetone and isopropyl alcohol. A 32 factorial design was adopted to optimize the formulation variables like, ratio of ethyl cellulose to pectin (X1) and coat weight (X2). The rate and extent of drug release were found to be related to the thickness and the ratio of pectin to ethyl cellulose within the film. Statistical treatments to the drug release data revealed that the X1 variable was more important than X2. Under simulated colonic conditions, drug release was more pronounced from coating formulations containing higher proportions of pectin. The surface of the device was coated with Eudragit S100 to ensure that the device was more pH dependent and trigger the drug release only at higher pH. The final product is expected to have the advantage of being biodegradable and pH dependant. This type of a film effectively releases the drug while maintaining its integrity.

Preparation and in vitro characterization of gellan based floating beads of acetohydroxamic acid for eradication of H. pylori

Gellan based floating beads of acetohydroxamic acid (AHA) were prepared by the ionotropic gellation method to achieve controlled and sustained drug release for treatment of Helicobacter pylori infection. The prepared beads were evaluated for diameter, surface morphology and encapsulation efficiency. Formulation parameters like concentrations of gellan, chitosan, calcium carbonate and the drug influenced the in vitro drug release characteristics of beads. Drug and polymer interaction studies were carried out using differential scanning calorimetry. Chitosan coating increased encapsulation efficiency of the beads and reduced the initial burst release of the drug from the beads. Kinetic treatment of the drug release data revealed a matrix diffusion mechanism. Prepared floating beads showed good antimicrobial activity (in vitro H. pylori culture) as potent urease inhibitors. In conclusion, an oral dosage form of floating gellan beads containing AHA may form a useful stomach site specific drug delivery system for the treatment of H. pylori infection.

Characterization of Biodegradable Poly(D,L-Lactide-co-Glycolide) Nanoparticles Loaded with Bacteriochlorophyll-a for Photodynamic Therapy

Bacteriochlorophyll-a (BChl-a) was incorporated into nanoparticles of poly(D,L-lactide-co-glycolide) (PLGA), in order to evaluate this photosensitizer when associated with this specific drug delivery system (DDS) to analyze its physical and spectral properties. It has been suggested in the literature that BChl-a is a potential sensitizer in photodynamic tumor therapy and until now has only been investigated in organic media. Nanoparticles loaded with the photosensitizer BChl-a were prepared by the solvent evaporation technique. Parameters such as particle size, drug encapsulation efficiency, external morphology, and in vitro release behavior were evaluated. The photophysical properties (absorption, fluorescence, fluorescence quantum yields, and singlet oxygen quantum yields) of BChl-a, were investigated in toluene and when encapsulated in nanoparticles. Scanning electron microscopy and dynamic light scattering revealed that particles loaded with BChl-a are spherical in shape, and they have a diameter of 660 nm and a low tendency to aggregate. The encapsulation efficiency obtained in this procedure was 69%. Spectroscopic analysis showed an absorption band centered at 782 nm in nanoparticles used as a DDS. Fluorescence quantum yield (phi(F) = 0.19) and higher efficiency in singlet oxygen production (Phi(Delta) = 0.26) was also observed. The results suggest that this DDS is potentially useful for the delivery and release of BChl-a as a photosensitizer in photodynamic therapy (PDT) protocols due to its excellent biodegradability, biocompatibility, and maintenance of its spectroscopic properties when compared with other dyes in homogenous media. The biocompatible DDS medium is a new proposal and will make feasible the use of BChl-a as a dye for PDT, improving the utilization of non-organic media to deliver this kind of molecule.

New Opioid Formulations and Delivery Systems

With the exception of tramadol, there have been no new opioid compounds added to the pain management armamentarium in the last 15 to 20 years. Yet, an array of new drug formulations and delivery systems have been developed that may help further individualize analgesic regimens for those patients who have acute and chronic pain. It is important to be aware of the full range of analgesic options available to best address a patient’s specific needs. Until recently, pain management pharmacotherapies were primarily limited to short-acting opioid formulations or only those opioids with inherently longer durations of action. The development of technologies that can control the release and slow absorption of a drug to provide an extended duration of action has led to significant potential benefits for patients with chronic pain who require continuous around-the-clock analgesia. Drugs with the lowest side effect profile for each individual and a formulation that best matches the pattern of pain should be given preference. An understanding of the indications, contraindications, onset, peak, and duration of action of specific drug formulations and delivery systems, as well as differences in individual opioids, is essential for providing effective pain control. Nurses play a pivotal role in counseling and patient education, as well as the ongoing reassessments to check how the patient is actually taking the medicine, the effectiveness of the agent, and the side effects. It is critical that nurses keep up to date with information on emerging formulations and opioid delivery technologies to administer safe and effective analgesia.

Production of bionanocapsules in immobilized insect cell culture using porous biomass support particles

L particles, composed of the L protein of the hepatitis B virus surface antigen, are candidates for a specific gene and drug delivery system. We previously constructed stably transfected insect cells for L particle production. In this study, the cells were successfully immobilized within porous biomass support particles (BSPs) in shake-flask culture. The immobilized cells showed a high specific productivity, comparable to the maximum productivities in static and shake-flask cultures of nonimmobilized cells.

Development of gelatin nanoparticles with biotinylated EGF conjugation for lung cancer targeting

Since lung cancer is the most malignant cancer today, a specific drug-delivery system has been developed for superior outcome. In this study, gelatin nanoparticles (GPs) employed as native carriers were grafted with NeutrAvidin FITC on the particle's surface (GP–Av). Next, the biotinylated epithelial growth factor (EGF) molecules were conjugated with NeutrAvidin FITC, forming a core-shell-like structure (GP–Av–bEGF) to achieve the enhancement of targeting efficiency. These nanoparticles were applied as an EGF receptor (EGFR)-seeking agent to detect lung adenocarcinoma. The results showed that the modification process had no significant influence on particle size (220 nm) and zeta potential (−9.3 mV). By the in vitro cell culture test, GP–Av–bEGF resulted in higher entrance efficiency on adenocarcinoma cells (A549) than that on normal lung cells (HFL1) because A549 possessed greater amounts of EGFR. We also found that uptake of GP–Av–bEGF by A549 cells was time and dose dependent. Confocal microscopy confirmed the cellular internalization of GP–Av–bEGF, and more fluorescent spots of GP–Av–bEGF nanoparticles were obviously observed as well as lysosomal entrapment in A549. Finally, the delivery was demonstrated by in vivo aerosol administration to cancerous lung of the SCID mice model, and specific accumulation in cancerous lung was confirmed by image quantification. The targeting ability of GP–Av–bEGF was proved in vitro and in vivo, which holds promise for further anti-cancer drug applications.

Circadian blood pressure: Clinical implications based on the pathophysiology of its variability

The circadian blood pressure (BP) rhythm is associated with worsened cardiovascular outcomes in patients who have an excessive morning BP surge and in those who lack the normal nocturnal BP fall (non-dippers). There are multiple pathophysiologic mechanisms underlying abnormalities in circadian BP, most importantly abnormalities in sympathetic nervous system activity, salt and volume balance, and activation of the renin-angiotensin system. Several of these factors can be modified by clinical interventions, either related to lifestyle changes and/or antihypertensive drug therapy. The timing of drug administration or specific drug delivery systems that lead to a greater effect at night and/or mitigate the early morning BP surge can correct abnormal circadian rhythms. Although these strategies have not yet been shown to alter clinical outcomes, it is reasonable to understand their biologic basis and take them into consideration when designing antihypertensive therapy.

Towards a correlation between drug properties and in vitro transdermal flux variability

Over recent years, there has been growing evidence that the permeability coefficient variability describing any specific transdermal drug delivery system is not always normally distributed. However, since different researchers have used different test compounds, methodologies and skin types, it has been difficult to identify any general correlation between drug properties and flux variability. The aim of the present study was to investigate whether there was a relationship between these two variables. To this end, six different compounds (sucrose, adenosine, aldosterone, corticosterone, oestradiol and testosterone) exhibiting a range of partition coefficients but relatively similar molecular weights were screened by taking multiple replicate measurements of their permeation profiles as they penetrated across porcine skin in vitro. It was found that for relatively hydrophilic solutes (log P o/w ≤ ∼2.5), physicochemical properties that facilitated slow transdermal flux were associated with more positively skewed permeability coefficient distributions while rapid flux was associated with more symmetric distributions. However, no correlation could be found between molecular properties and the extent of statistical fit to either the normal or log-normal distribution.

AZT and AZT-monophosphate Prodrugs Incorporating HIV-protease Substrate Fragment: Synthesis and Evaluation as Specific Drug Delivery Systems

With the view to deliver anti-HIV nucleoside and nucleoside-monophosphate (MP) analogues specifically into HIV-infected cells, we synthesized a series of ester and phosphoramidate peptide conjugates of zidovudine (AZT) and of AZT-MP, respectively, wherein the peptide sequences derive from a HIV-protease (PR) hydrolysable substrate. Their in vitro stability with respect to hydrolysis, anti-HIV activity and cytotoxicity, and ability to inhibit the HIV-PR activity were investigated. Concerning the ester AZT-peptide conjugates, their antiviral activity level in thymidine kinase-expressing (TK+) CEM-SS and MT-4 cells was in most cases closely correlated to their hydrolysis rate: the faster the hydrolysis, the closer the anti-HIV activity to that of AZT. None of them was a HIV-PR substrate, indicating that their antiviral activity was not related to their intracellular hydrolysis by this enzyme. None of them inhibited HIV in TK-deficient (TK-) CEM cells, demonstrating that they probably act as prodrugs of AZT. Most of the phosphoramidate peptide conjugates of AZT-MP were rapidly degraded in a physiological buffer into several metabolites including AZT. Their anti-HIV activity in TK+ CEM-SS and MT-4 cells was much lower than that of AZT, indicating that only low amounts of AZT or AZT-MP were released into cells during incubation. Antiviral activities measured on TK- CEM cells for some phosphoramidates suggest that low amounts of AZT-MP could be released intracellularly. However, this AZT-MP release was not initiated by a HIV-PR hydrolysis, as no evidence for peptide cleavage was obtained by HPLC analysis of one representative compound after incubation with HIV-PR.

Design and evaluation of colon specific drug delivery system containing flurbiprofen microsponges

The purpose of this study was to design novel colon specific drug delivery system containing flurbiprofen (FLB) microsponges. Microsponges containing FLB and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. Additionally, FLB was entrapped into a commercial Microsponge ® 5640 system using entrapment method. Afterwards, the effects of drug:polymer ratio, inner phase solvent amount, stirring time and speed and stirrer type on the physical characteristics of microsponges were investigated. The thermal behaviour, surface morphology, particle size and pore structure of microsponges were examined. The colon specific formulations were prepared by compression coating and also pore plugging of microsponges with pectin:hydroxypropylmethyl cellulose (HPMC) mixture followed by tabletting. In vitro dissolution studies were done on all formulations and the results were kinetically and statistically evaluated. The microsponges were spherical in shape, between 30.7 and 94.5 μm in diameter and showed high porosity values (61–72%). The pore shapes of microsponges prepared by quasi-emulsion solvent diffusion method and entrapment method were found as spherical and cylindrical holes, respectively. Mechanically strong tablets prepared for colon specific drug delivery were obtained owing to the plastic deformation of sponge-like structure of microsponges. In vitro studies exhibited that compression coated colon specific tablet formulations started to release the drug at the 8th hour corresponding to the proximal colon arrival time due to the addition of enzyme, following a modified release pattern while the drug release from the colon specific formulations prepared by pore plugging the microsponges showed an increase at the 8th hour which was the time point that the enzyme addition made. This study presents a new approach based on microsponges for colon specific drug delivery.

New Drug Delivery for Corneal Neovascularization Using Polyion Complex Micelles

To introduce photodynamic therapy (PDT) for corneal neovascularization (NV) by polyion complex (PIC) micelles, a novel drug delivery system. Development of specific drug delivery systems to corneal NV sites is an important part of next-generation photodynamic therapy. Nanocarriers consisting of PIC micelles bound by polyethylene glycol (PEG) shell exhibit good stability, high drug-loading capacity, and excellent potential for controlled drug release. Encapsulation of the photosensitizer dendrimer porphyrin (DP) into PIC micelles (DP-micelles) conveys adequate stability and increased photocytotoxicity without compromising photophysical properties of DP stability. We assessed the accumulation of DP-micelles and observed that the DP-micelles were incorporated into the corneal NV area. PIC micelles possess attractive features of selective accumulation at the corneal NV site. PDT using DP-micelles appears to be effective and safe for the treatment of corneal NV.

DNA helps dendrimers branch out

DNA offers a direct and specific way to link dendrimer beads, demonstrating the potential for developing specialized drug delivery systems via multibead assemblies.

Accelerating tissue expansion by application of topical papaverine cream.

The rate of tissue expansion can be accelerated by papaverine through a special delivery system, according to an early report. Because the delivery system was complex and inconvenient, another means of administrating papaverine was tested to observe the rate of tissue expansion. In this study, 24 miniature pigs were divided equally into three groups. Four 150-ml silicone expanders were implanted into each pig in groups A and C. Four modified rectangular silicone expanders were also implanted into each animal in group B. During the expansion process, 1 g of 2% hydrochloride papaverine cream was applied topically onto the surface of each pig's expanding skin in group A two times daily, and hydrochloride papaverine solution was injected into the outer shell of each modified expander in group B weekly. Group C acted as the control group. The mean sum of the first four times of saline water volume that was injected into the expanders was 142.42 +/- 5.6 ml in group A, 128.72+/-4.8 ml in group B, and 106.38+/-3.28 in group C. There were statistical differences among the three groups. The mean sum of volume saline water that was injected into hind expanders was 137.51 +/- 5.1 ml in group A, 120.35 +/- 3.6 ml in group B, and 102.63 +/- 4.76 ml in group C, and there was a statistical difference among the three groups as well. There was no statistically significant difference in the thickness of fibrous capsules among the three groups. This study shows that the rate of tissue expansion can be accelerated by topical application of papaverine cream, and the rate is better than the rate of tissue expansion induced by the special drug delivery system.

Matrix- and Reservoir-Based Transmucosal Delivery Systems

Traditionally, per-oral delivery has been the primary route of administration for therapeutic agents targeting systemic delivery. However, oral administration subjects these compounds to extensive presystemic elimination, which may include gastrointestinal degradation, metabolism, or first-pass clearance via the liver, and may ultimately result in poor bioavailability. Parenteral routes, such as intravenous or intramuscular, permit therapeutic agents to gain direct entry into the systemic circulation and, therefore, reach the intended site of action more rapidly. Unfortunately, this mode of drug administration entails numerous disadvantages, including the requirement for close medical supervision and the need for specialized equipment. Transmucosal absorption of nitroglycerin from solutions through the oral cavity was demonstrated in the mid-nineteenth century, and since that time various conventional drug delivery systems for oral mucosal delivery have been proposed and have achieved clinical application. Technologic advances in biomaterials and techniques have resulted in the formulation of novel designs more pertinent to the oral cavity, meeting the challenges of the physicochemical properties of the drug entity itself and achieving the therapeutic aims of the drug delivery system. Issues of patient compliance and convenience have recently resulted in a trend toward once-a-day administration regimens, requiring drugs with high potency and sustained effect. Such drugs usually have a short biologic half-life, exhibit poor permeability and solubility, and are susceptible to enzymatic degradation. However, because of the advantages of delivering a drug through the oral mucosa, these drugs are viable candidates for delivery via this route. Many investigators have studied the potential of transmucosal delivery through the oral cavity, and the oral mucosa is increasingly being considered as a plausible route for many drug classes. Sublingual tablets, oral lozenges, chewing gum systems, and other dosage forms represent potential drug delivery systems for the oral mucosa, but most of the literature has not discussed information on specific drug delivery systems and their challenges. This article examines the anatomy, physiology, and absorption properties of the oral mucosal environment; explores the considerations for a transmucosal system; reviews these types of systems; and evaluates and proposes matrix and reservoir transmucosal applications.

In vitro and in vivo evaluations of THAM derived telomers bearing RGD and Ara-C for tumour neovasculature targeting

As an approach to the development of specific drug delivery systems, a new class of low macromolecular carriers called ‘telomers’ endowed with an antitumour agent, such as arabinofuranosylcytosine (Ara-C), RGDSK peptidic sequences, as tumour targeting moieties, and tyrosine groups labelled with 125I atoms allowing the in vivo scintigraphic follow up, were synthesized. Their tumour targeting ability was assessed in vivo in mice bearing a murine B16 melanoma. The biological results showed that the presence of RGDSK sequences onto the macromolecules leads to the selective targeting and the accumulation of telomers within the vascularized zone of the tumour. Moreover, such compounds exhibited in vitro a better IC50 (0.015 μM) than pure Ara-C and in vivo an oncostatic index higher than 160%.

Peptido- and glycocalixarenes: playing with hydrogen bonds around hydrophobic cavities.

This Account reviews the synthesis, conformations, and supramolecular properties of calixarenes endowed with alpha-amino acids or peptides (Peptidocalixarenes) and carbohydrate units (Glycocalixarenes), with a major emphasis on calix[4]arenes functionalized on the aromatic nuclei (upper or wide rim). Most properties of N-linked peptidocalix[4]arenes are found to be quite different from those of the corresponding C-linked derivatives. An interesting example is the tendency of C-linked peptidocalix[4]arenes to form self-assembled nanotubes in the solid state. In several cases the hydrogen bonding donor and acceptor groups of the amino acid residues and the cavity of cone calix[4]arenes act cooperatively in guest binding in nonpolar solvents but not in water, where hydrophobic interactions dominate. Upper-rim bridged peptidocalix[4]arenes act as vancomycin mimics being able to bind d-alanyl-d-alanine (d-Ala-d-Ala) residues. Glycocalix[4]arenes show the phenomenon of multivalency in their binding to specific lectins, and those bearing thiourea spacers between the calix[4]arene scaffold and the sugar units are able to bind aromatic carboxylates and phosphates, making them attractive as novel site specific drug delivery systems.

Binders for colon specific drug delivery: an in vitro evaluation

The aim of the present study was to develop a single unit, site-specific drug formulation allowing targeted drug release in the colon. Tablets were prepared using polysaccharides or synthetic polymer as binders. These included xanthan gum, guar gum, chitosan and Eudragit E. Indomethacin was used as a model drug. The prepared tablets were enteric coated with Eudragit-L 100 to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The drug release studies were carried out in simulated stomach environment (pH 1.2) for 2 h followed by small intestinal environment at pH 6.8. The dissolution data obtained from tablets demonstrates that the dissolution rate of the tablet is dependent upon the type and concentration of polysaccharide/polymer used as binder. The results demonstrate that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using guar gum as binder, were unable to protect drug release under similar conditions. Preparations with xanthan gum as a binder formed time-dependent release formulations. When used in a concentration of 5.92% in the tablets, 28% drug release was observed in the usual upper gastrointestinal tract conditions. It was also found that enteric coated preparation formulated with 8.88% of Eudragit E as binder could be used to carry water insoluble drug molecules to the colon especially in IBD. The above study shows that chitosan could be successfully used as a binder, for colon targeting of water insoluble drugs in preference to guar gum when used in the same concentration. Additionally, formulations developed with chitosan and Eudragit E would be highly site specific since drug release would be at a retarded rate till microbial degradation or polymer solubilization takes place in the colon.

Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells.

Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity in vivo limit its delivery to cancer cells. To increase the anticancer efficacy of CPT a special drug delivery system is needed. To synthesize a novel camptothecin-poly(ethylene glycol) conjugate (CPT-PEG) which includes biotin as a moiety to enhance nonspecific and/or targeted uptake via the sodium-dependent multivitamin transporter (SMVT) and to evaluate its anticancer activity and apoptosis induction. CPT-PEG and CPT-PEG-biotin conjugates were synthesized and studied in vitro in A2780 sensitive and A2780/AD multidrug-resistant human ovarian carcinoma cells. Cytotoxicity, apoptosis induction, expression of genes encoding BCL-2 and apoptotic protease-activating factor 1 (APAF-1) proteins and caspases 3 and 9 as well as caspase activity were measured.RESULTS. We found that the conjugation of CPT with a simple linear PEG polymer led to a more than 12-fold enhancement of CPT toxicity in both sensitive and multidrug-resistant cells. Biotinylation of the PEG led to a further increase in CPT toxicity (5.2 times in sensitive and 2.1 times in multidrug-resistant cells) compared to the nonbiotinylated CPT-PEG conjugate. As a result, the cytotoxicity of the CPT-PEG-biotin conjugate increased more than 60 times in sensitive and almost 30 times in resistant cells, probably by enhancing nonspecific passive and/or SMVT-mediated uptake. In contrast, the same amounts of PEG and PEG-biotin conjugates without CPT did not induce cell death in either sensitive or resistant cells. Further analysis showed that the biotinylated CPT-PEG conjugate induced apoptosis more significantly than the same equivalent concentrations of free CPT or nonbiotinylated CPT-PEG. The enhancement of proapoptotic activity was achieved by the overexpression of genes encoding the APAF-1, and caspases 3 and 9, increasing caspase activity and simultaneously downregulating the BCL-2 gene. The results obtained demonstrate that the binding of CPT to PEG/PEG-biotin polymers increases its cytotoxicity, ability to induce apoptosis by the activation of caspase-dependent cell death signaling pathway and simultaneous suppression of antiapoptotic cellular defense. This suggests that the targeting approach utilizing transporters such as SMVT may substantially improve the delivery of CPT and its anticancer activity by enhancing cellular permeability and possibly retention of CPT.

Chitin/PLGA blend microspheres as a biodegradable drug-delivery system: phase-separation, degradation and release behavior

A novel chitin-based microsphere was developed for anti-cancer drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with different contents of poly( d, l-lactide-co-glycolide 50:50) (PLGA 50/50) in dimethylacetamide–lithium chloride solution, and following it by coagulating in water via wet phase inversion. Scanning electron microscopy (SEM) micrography of the blend microsphere showed that there are numerous PLGA particulates homogeneously dispersed in chitin matrix, suggesting the occurrence of obvious phase separation from the blended chitin and PLGA 50/50 phase due to their thermodynamic incompatibility. Degradation of the chitin/PLGA 50/50 blend microsphere depends on the surface erosion of chitin phase and bulk hydrolysis of PLGA phase, according to the examinations of SEM and differential scanning calorimetry studies. Weight loss of the chitin/PLGA 50/50 blend microsphere increases with the increase of chitin content in the microsphere. A two-phase drug-release model is observed from the release of chlorambucil from chitin/PLGA 50/50 blend microspheres. The initial stage of drug-release rate increases with the increased chitin content due to the hydration and surface erosion of hydrophilic chitin phase; however, the following stage of slow release is sustained for several days, mainly contributed by the bulk hydrolysis of hydrophobic PLGA phase. In conclusion, such a chitin/PLGA 50/50 blend microsphere is novel and interesting, and may be used as a special drug-delivery system.

Preferential binding of polyethylene glycol-coated liposomes containing a novel cationic lipid, TRX-20, to human subendthelial cells via chondroitin sulfate.

To design novel cationic liposomes, polyethylene glycol (PEG)-coated cationic liposomes containing a newly synthesized cationic lipid, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) were formulated and their cellular binding and uptake investigated in vitro in the following cells: human subendothelial cells (aortic smooth muscle cells and mesangial cells) and human endothelial cells. Three different PEG-coated cationic liposomes were prepared by the extrusion method, and their mean particle size and zeta potential were determined. Rhodamine-labeled PEG-coated cationic liposomes were incubated with smooth muscle cells, mesangial cells, and endothelial cells at 37 degrees C for 24 h. The amounts of cellular binding and uptake of liposomes were estimated by measuring the cell-associated fluorescence intensity of rhodamine. To investigate the binding property of the liposomes, the changes of the binding to the cells pretreated by various kinds of glycosaminoglycan lyases were examined. Fluorescence microscopy-is used to seek localization of liposomes in the cells. The cellular binding and uptake of PEG-coated cationic liposomes to smooth muscle cells was depended strongly on the chemical species of cationic lipids in these liposomes. Smooth muscle cells bound higher amount of PEG-coated TRX-20 liposomes than other cationic liposomes containing N-(1-(2.3-dioleoyloxy) propyl)-N, N, N-trimethylammonium salts or N-(alpha-(trimethylammonio)acetyl)-D-glutamate chloride. Despite of the higher affinity of PEG-coated TRX-20 liposomes for subendothelial cells, their binding to endothelial cells was very small. The binding to subendothelial cells was inhibited when cells were pretreated by certain kinds of chondroitinase, but not by heparitinase. These results suggest that PEG-coated TRX-20 liposomes have strong and selective binding property to subendothelial cells by interacting with certain kinds of chondroitin sulfate proteoglycans (not with heparan sulfate proteoglycans) on the cell surface and in the extracellular matrix of the cells. This binding feature was different from that reported for other cationic liposomes. PEG-coated TRX-20 liposomes can strongly and selectively bind to subendothelial cells via certain kinds of chondroitin sulfate proteoglycans and would have an advantage to use as a specific drug delivery system.