Surface Modification Of Liposomes Research Articles

Retinal drug delivery using eyedrop preparations of poly-l-lysine-modified liposomes

The purpose of this study was to develop surface-modified liposomes that enhance the efficiency of eye drop drug delivery to the retina. Various molecular weights and concentrations of the water-soluble cationic polymer poly-l-lysine (PLL) were used to modify the surface of submicronized (100nm) liposomes. Physicochemical properties of surface-modified liposomes were determined in vitro, and the efficiency of drug delivery to the retina was investigated in vivo. Using coumarin-6 as a model drug and fluorescent marker, we show that liposome surface modification by PLL dramatically increased delivery to mouse retina segments after eye drop administration. However, when PLL of high molecular weight (>30,000) was used at higher concentrations (>0.05%), aggregation of surface-modified liposomes increased particle size and hampered distribution to inner ocular tissues. As a result, the efficiency of drug delivery of these aggregated surface-modified liposomes was the same as unmodified liposomes. The optimal molecular weight and concentration of PLL in drug-delivering liposomes were 15,000–30,000 and 0.005%, respectively. Under these conditions, PLL-modified liposomes were not cytotoxic in corneal or conjunctival cells. In conclusion, surface-modified liposomes have great potential as effective retinal drug delivery carriers in eye drop formulations.

Enhanced Pharmacokinetics and Anti-Tumor Efficacy of PEGylated Liposomal Rhaponticin and Plasma Protein Binding Ability of Rhaponticin

Rhaponticin (RA) extracted from many medicinal plants has been demonstrated to possess a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant activities. However, its poor solubility and bioavailability restricted the clinical application greatly. In this work, surface modification of liposome with polyethylene glycol (PEG) was developed with the purpose of improving the pharmacokinetics and anti-tumor efficacy of RA. PEGylated liposomal RA (PEGL-RA) was prepared by dry-film method. Its mean particle size was 89.3 +/- 8.7 nm, mean zeta potential was -4.1 mV and encapsulation efficiency was 67.4 +/- 6.4%. Moreover, the results of pharmacokinetic analysis showed that the time of maximum plasma concentration (Tmax) of PEGL-RA was about 4.5 times higher than that of free RA after oral administration due to the lower distribution into the gastrointestinal tract. The mean T1/2 value of PEGL-RA and free RA were 350.12 +/- 0.87 min and 180.02 +/- 1.96 min, respectively. The AUC0-->infinity ratio of PEGL-RA to free RA was about 2.41-fold (93.23 microg/mLmin/40.81 microg/mLmin). Plasma protein binding ability of RA was also studied. The results showed that RA with 33.6 microg/mL concentrations in human plasma and HSA achieved the percent of bound 39.23 +/- 3.78% and 22.28 +/- 2.34%, respectively. In the in vivo studies utilizing solid tumor-bearing rat, it was confirmed that PEGL-RA delivered remarkably larger amount of RA to tumor tissue and provided more significant anti-tumor activity than free RA. Furthermore, the cytotoxicity and fluorescence microscopic studies showed higher intracellular uptake of PEGL-RA than that of RA. In conclusion, PEGylated liposome was an effective delivery formulation for RA to increase the pharmacokinetics and therapeutic efficacy.

Characterization of fatty acid liposome coated with low-molecular-weight chitosan

Preparation of chitosan-coated fatty acid liposomes is often restricted by the solubility of chitosan under basic conditions. In this experiment, the preparation of chitosan-coated oleic acid (OA) liposomes using low molecular weight (LMW) chitosan (10 and 25 kDA) was demonstrated. These selected LMW chitosans are water soluble. The coating of the chitosan layer on OA liposomes was confirmed by its microscope images and physicochemical properties, such as zeta potential and the size of the liposomes. The “peeling off” effect on the surface of chitosan-coated OA liposomes was observed in the atomic force microscope images and showed the occurrence of the chitosan layer on the surface of OA liposomes. The size of the chitosan-coated liposomes was at least 20 nm smaller than the OA liposomes, and the increase of zeta potential with the increasing amount of LMW chitosan further confirmed the presence of the surface modification of OA liposomes.

A Novel Liposome Surface Modification Agent that Prolongs Blood Circulation and Retains Surface Ligand Reactivity

Liposomes are recognized as potentially useful drug carriers but many problems preclude practical medical application. Liposomes bind with serum proteins (opsonization) and are captured by the reticuloendothelial system cells in the liver and spleen, which limits their ability to deliver drugs to other target sites. Modification of lipids with flexible, hydrophilic polymers such as poly(ethylene glycol) (PEG) to yield sterically stabilized liposomes is one approach to improve liposome blood circulation and tissue distribution properties. In this study, we examined liposomes prepared using lipids modified with a new branched oligoglycerol (BGL) moiety for steric stabilization. This novel BGL comprised 14 glycerol units (termed BGL014) connected with flexible ether linkages, resulting in a branched cascade-like structure that is highly expanded in aqueous solution. BGL014 was coupled to 1,2-distearoylphosphatidylethanolamine to yield BGL014-modified lipids. Incorporation of BGL014 into liposomes (BGL014L) resulted in long blood circulation times, despite a much thinner fixed aqueous layer thickness compared to PEG formulations. BGL014 produced a liposome surface coating that appears to function through steric inhibition of non-specific protein binding without strong interference of specific protein-binding reactions. Liposome structure and functionality was maintained following BGL014-modification, as the incorporation ratio of drug remained high. These results suggest that the BGL014 modification of liposomes is a promising approach to produce stable and long circulating drug carriers capable of selective binding to specific proteins.

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.

Pulmonary delivery of elcatonin using surface-modified liposomes to improve systemic absorption: Polyvinyl alcohol with a hydrophobic anchor and chitosan oligosaccharide as effective surface modifiers

The aim of this study was to investigate the feasibility of surface-modified liposomes for pulmonary delivery of a peptide. Chitosan oligosaccharide (oligoCS) and polyvinyl alcohol with a hydrophobic anchor (PVA-R) were used as surface modifiers. The effect of liposomal surface modification on the behavior of the liposomes on pulmonary administration and potential toxicity were evaluated in vitro and in vivo. In an association study with A549 cells, PVA-R modification reduced interaction with A549 cells, whereas oligoCS modification electrostatically enhanced cellular interaction. The therapeutic efficacy of elcatonin (eCT) after pulmonary administration to rats was significantly enhanced and prolonged for 48h after separate administration with oligoCS- or PVA-R-modified liposomes. oligoCS-modified liposomes adhered to lung tissues and caused opening of tight junctions, which enhanced eCT absorption. On the other hand, PVA-R-modified liposomes induced long-term retention of eCT in the lung fluid, leading to sustained absorption. Consequently, surface modification of liposomes with oligoCS or PVA-R has potential for effective peptide drug delivery through pulmonary administration.

Research Highlights

Research Highlights

Surface modification of liposomes with rhodamine-123-conjugated polymer results in enhanced mitochondrial targeting

A novel mitochondrial-targeted liposomal drug-delivery system was prepared by modification of the liposomal surface with a newly synthesized polymer, rhodamine-123 (Rh123)-PEG-DOPE inserted into the liposomal lipid bilayer. This novel polymer was synthesized by conjugating the mitochondriotropic dye Rh123, with the amphiphilic polyethylene glycol–phosphatidylethanolamine (PEG-PE) conjugate. The modified liposomes showed better uptake by cells (HeLa, B16F10) estimated by fluorescence microscopy and FACS analysis. The co-localization study with stained mitochondria as well as with the isolation of mitochondria of the cultured cells after their treatment with Rh123 liposomes showed a high degree of accumulation of the modified liposomes in the mitochondria. We also prepared mitochondrial-targeted and nontargeted paclitaxel (PCL)-loaded liposomes. Mitochondrial-targeted PCL-loaded liposomes demonstrated enhanced cytotoxicity toward cancer cells compared with nontargeted drug-loaded liposomes or free PCL. Thus, Rh123-modified liposomes target mitochondria efficiently and can facilitate the delivery of a therapeutic payload to mitochondria.

Chitosan-coated liposomes for intracellular oligonucleotides delivery: Characteristics and cell uptake behavior

Surface modification of liposomes with polymer to optimize drug delivery was well developed recently. The objective of the present work was to evaluate the feasibility of chitosan-coated liposomes (CSLP) as vehicles for anti-sense oligodeoxynucleotides (ASON). CSLP was obtained by adding chitosan dropwise to liposomes under magnetic stirring. The effect of chitosan content on size, zeta potential, and coating efficiency was investigated, which showed that chitosan increased the size and zeta potential of CSLP, and the coating efficiency increased with chitosan content increasing. Agarose gel electrophoresis was employed to evaluate the loading efficiency of CSLP for ASON, from which one could see ASON was completely combined to CSLP when the mass ratio of total lipids:ASON was more than 50:1. MTT assay showed that CSLP took on very low cytotoxicity, which is much lower than chitosan. At last, cell uptake behavior was investigated by a flow cytometer, which showed that CSLP enhanced significantly the COS7 cells uptake of ASON. All the results indicated that the CSLP could be a promising non-viral ASON vehicle.

高分子の表面修飾による機能性リポソームの設計

For establishment of safe and effective therapy, carriers that achieve high-precision drug delivery are required. Liposomes are one of the most promising drug delivery systems. To increase usefulness of liposomes as drug delivery systems, we have attempted to provide various functions to liposomes via surface surface modification of liposomes with functional polymers. Functions of polymer-modified liposomes were based on their interactions. Therefore, surface-modification of liposomes with temperature-sensitive polymers can give temperature-responsive liposomes whose drug release is triggered by mild heating. Also, surface modification of liposomes with pH-sensitive polymers can generate pH-responsive liposomes whose destabilization is induced in weakly acidic environments. In addition, modification with several kinds of polymers with different functions can generate multifunctional liposomes. Here, we describe design, preparation and performance of functional liposomes based on the surface modification with functional polymers, such as temperature-sensitive, pH-sensitive, magnetic resonance-detectable polymers for the production of liposomes for high-precision site-specific delivery and/or intracellular delivery of bioactive molecules.

Modification of liposome surface with pH-responsive polyampholytes for the controlled-release of drugs

Ampholytic polymers comprised of 2-(diethylamino)ethyl methacrylate (DEAEMA) and acrylic acid (AA) in varying molar ratios were used to modify egg yolk phosphatidylcholine (EYPC) liposomes previously encapsulated with pyranine. The modified EYPC liposomes were found to be pH responsive. The critical pH values at which the pyranine release from these liposomes at 37 °C were observed to decrease with increasing DEAEMA content in the polymers. Explanations were given for these phenomena.

Surface Modification of Pharmaceutical Nanocarriers with Ascorbate Residues Improves their Tumor-Cell Association and Killing and the Cytotoxic Action of Encapsulated Paclitaxel In Vitro

To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity. Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells with GFP expressing non-cancer cells was used to determine the specificity of palmitoyl ascorbate liposome binding. Liposomes were fluorescently labeled to facilitate analysis by flow cytometry and fluorescence microscopy. The cytotoxic action of palmitoyl ascorbate liposomes against a variety of cell types was assayed using a standard metabolic assay. The cytotoxic effect of a low dose of paclitaxel incorporated in palmitoyl ascorbate liposomes on various cell lines was also determined. Palmitoyl ascorbate liposomes associated preferentially with various cancer cells compared to non-cancer cells in a co-culture model. Palmitoyl ascorbate liposomes exhibited anti-cancer toxicity in numerous cancer cell lines. Furthermore, ascorbate liposomes enhanced the effectiveness of encapsulated paclitaxel compared to paclitaxel encapsulated in 'plain' liposomes. Surface modification of liposomes with ascorbate residues represents a novel way to target and kill certain types of tumor cells and additionally can potentiate the effect of paclitaxel delivered by the liposomes.

Biomimetic Glycoliposomes as Nanocarriers for Targeting P-Selectin on Activated Platelets

The cell glycocalyx is an attractive model for surface modification of liposomes with the objectives of tissue targeting and prolonged circulation time. Here, we reported on glycocalyx-mimicking liposomes, prepared by incorporating a glycolipid of 3'-sulfo-Lewis a (SuLe(a))-PEG-DSPE with a headgroup of SuLe(a) and a spacer of poly(ethylene glycol) (PEG) linked to two hydrophobic tails. This PEG spaced structure is used to mimic the extended structure of P-selectin glycoprotein ligand 1 (PSGL-1) on activated leukocytes, in order to facilitate the specific binding of liposomes to the receptor of P-selectin expressed on activated platelets. Our results indicate that SuLe(a)-PEG-DSPE can form stable, narrowly distributed liposomes with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, with a vesicle size of 113.3 nm. The resultant SuLe(a)-PEG-liposomes can facilitate their binding to the receptor of P-selectin 22 times higher than SuLe(a)-liposomes without a PEG spacer. Further studies by fluorescence microscopy show that SuLe(a)-PEG-liposomes can bind to activated platelets in vitro effectively. It suggests that biomimetic SuLe(a)-PEG-liposomes may be used as nanocarriers to target activated platelets for drug delivery to the injury sites of cardiovascular diseases.

Vesicle size and stability of biomimetic liposomes from 3′-sulfo-Lewis a (SuLe a) containing glycolipids

We report on the use of a natural Lewis type saccharide ligand, 3′-sulfo-Lewis a (SuLe a) for glycocalyx-mimetic surface modification of liposomes. Two SuLe a-containing glycolipids, monovalent SuLe a-lipid and trivalent SuLe a (TSuLe a)-lipid, were synthesized, and used with 1,2-distearoyl- sn-glycero-3-phosphocholine (DSPC) and cholesterol to prepare unilaminar vesicles (ULVs) by a freeze–thaw and extrusion method. The effects of the glycolipid concentrations and the pore sizes of extrusion membranes on vesicle size and stability were investigated by photon correlation spectroscopy (PCS). Glycoliposomes, with 5% SuLe a- or TSuLe a-lipids obtained by 50 nm extrusion, had 25–30% more vesicles less than 100 nm in diameter compared with the 100 nm extrusion. TSuLe a-liposomes always produced larger vesicle size than SuLe a-liposomes, which we attribute to the larger TSuLe a headgroup. Both SuLe a- and TSuLe a-liposomes increased their vesicle size with increasing glycolipid concentration from 5% to 15%, and demonstrated good stability at room temperature for over 1 month. Further increasing the glycolipid concentration to 20% resulted in large vesicle aggregation after 5 days for TSuLe a-liposomes, while the SuLe a-liposomes remained stable for 10 days. SuLe a- and TSuLe a-liposomes with 15% glycolipids demonstrated better stability due to the electrostatic effect from the negatively charged SuLe a and TSuLe a headgroups. The results indicate that the biomimetic liposomes with SuLe a- and TSuLe a-lipids with 5 to 15% incorporation are sufficiently stable for the potential applications in targeted drug delivery.

Novel O-palmitoylscleroglucan-coated liposomes as drug carriers: Development, characterization and interaction with leuprolide

Polysaccharide-coated liposomes have been studied for their potential use for peptide drug delivery by the oral route because they are able to minimize the disruptive influences on peptide drugs of gastrointestinal fluids. The aim of this work was to synthesize and characterize a modified polysaccharide, O-palmitoylscleroglucan (PSCG), and to coate unilamellar liposomes for oral delivery of peptide drugs. To better evaluate the coating efficiency of PSCG, also scleroglucan (SCG)-coated liposomes were prepared. We studied the surface modification of liposomes and the SCG- and PSCG-coated liposomes were characterized in terms of size, shape, ζ potential, influence of polymer coating on bilayer fluidity, stability in serum, in simulated gastric and intestinal fluids and against sodium cholate and pancreatin. Leuprolide, a synthetic superpotent agonist of luteinizing hormone releasing hormone (LHRH) receptor, was chosen as a model peptide drug. After polymer coating the vesicle dimensions increased and the ζ potential shifted to less negative values. These results indicate that both SCG- and PSCG-coated liposomes surface and DSC results showed that PSCG was anchored on the liposomal surface. The stability of coated-liposomes in SGF, sodium cholate solution and pancreatin solution was increased. From this preliminary in vitro studies, it seems that PSCG-coated liposomes could be considered as a potential carrier for oral administration.

“SMART” Drug Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers

To develop targeted pharmaceutical carriers additionally capable of responding to certain local stimuli, such as decreased pH values in tumors or infarcts, targeted long-circulating PEGylated liposomes and PEG-phosphatidylethanolamine (PEG-PE)-based micelles have been prepared with several functions. First, they are capable of targeting a specific cell or organ by attaching the monoclonal antimyosin antibody 2G4 to their surface via pNP-PEG-PE moieties. Second, these liposomes and micelles were additionally modified with biotin or TAT peptide (TATp) moieties attached to the surface of the nanocarrier by using biotin-PE or TATp-PE or TATp-short PEG-PE derivatives. PEG-PE used for liposome surface modification or for micelle preparation was made degradable by inserting the pH-sensitive hydrazone bond between PEG and PE (PEG-Hz-PE). Under normal pH values, biotin and TATp functions on the surface of nanocarriers were "shielded" by long protecting PEG chains (pH-degradable PEG(2000)-PE or PEG(5000)-PE) or by even longer pNP-PEG-PE moieties used to attach antibodies to the nanocarrier (non-pH-degradable PEG(3400)-PE or PEG(5000)-PE). At pH 7.4-8.0, both liposomes and micelles demonstrated high specific binding with 2G4 antibody substrate, myosin, but very limited binding on an avidin column (biotin-containing nanocarriers) or internalization by NIH/3T3 or U-87 cells (TATp-containing nanocarriers). However, upon brief incubation (15-30 min) at lower pH values (pH 5.0-6.0), nanocarriers lost their protective PEG shell because of acidic hydrolysis of PEG-Hz-PE and acquired the ability to become strongly retained on an avidin column (biotin-containing nanocarriers) or effectively internalized by cells via TATp moieties (TATp-containing nanocarriers). We consider this result as the first step in the development of multifunctional stimuli-sensitive pharmaceutical nanocarriers.

혈류 내 안정성 향상을 위한 빗 모양 고분자로 개질된 리포솜

혈류 내에서 리포솜의 안정성을 향상시키기 위해 지질-고분자 유도체를 지질 이중층에 도입하거나 친수성 고분자를 리포솜에 결합시켜 리포솜의 표면을 개질하는 방법이 개발되어왔다. 본 연구에서는 비닐 단량체로서 히드록시에틸메타크릴레이트(HEMA)와 히드록시폴리옥시에틸렌메타크릴레이트(HPOEM)를 자유 라디칼 중합하여 측쇄에 다수의 폴리에틸렌옥사이드를 갖는 빗(Comb) 모양 공중합체인 poly(HEMA-co-HPOEM)를 제조하였다. Poly(HEMA-co-HPOEM)를 리포솜의 표면에 결합시키고 혈장 용액 내에서 개질된 리포솜의 특성을 살펴보았다. Poly(HEMA-co-HPOEM)으로 개질된 리포솜의 입자크기는 대조군 리포솜에 비해 약 30 nm 증가하였고 리포솜 표면의 음전하를 차폐하여 제타 포텐셜의 절대값은 감소하였다. 리포솜 내부에 모델약물인 독소루비신(Doxorubicin)의 로딩효율은 ~ 90%로서 리포솜 표면에 결합된 poly(HEMA-co-HPOEM)는 약물의 로딩효율에 영향을 주지 않았다. 혈장 내에서 리포솜의 안정성을 평가한 결과, 빗 모양 고분자로 수식한 리포솜의 입자크기는 증가하지 않았고 단백질 흡착은 대조군 리포솜 또는 폴리에틸렌옥사이드-지질 유도체가 도입된 리포솜(PEG-리포솜)에 비해 감소되어 빗 모양 고분자인 poly(HEMA-co-HPOEM)이 혈류 내 리포솜의 안정성 향상에 효과적임을 확인하였다. To increase the stability of liposomes in blood circulation, surface modification of liposomes by incorporating a lipid-polymer derivative in the lipid bilayer or conjugating a hydrophilic polymer to the liposomal surface has been developed. In this study, the comblike copolymer, poly(HEMA-co-HPOEM), having multiple polyethyleneoxide side chains was prepared by free radical polymerization of hydroxyethylmethacrylate (HEMA) and hydroxypolyoxyethylenemethacrylate (HPOEM) as vinyl monomers. Poly(HEMA-co-HPOEM) was conjugated to the liposomal surface and the characteristics of the modified liposomes in serum were investigated. Conjugation of poly(HEMA-co-HPOEM) to liposomes increased the particle size of the liposomes by 30 nm and decreased the absolute value of zeta potential of the liposomes by shielding the negative charge of liposomal surface. Loading efficiency of model drug, doxorubicin, in liposomes was about 90% and the efficiency was not affected by conjugation of poly(HEMA-co-HPOEM) to liposomes. The particle size of poly(HEMA-co-HPOEM)-conjugated liposomes in serum did not changed and the protein adsorption was lower than that of control liposomes or liposomes containing polyethyleneoxide-lipid derivative (PEG-liposomes). These results suggest that poly(HEMA-co-HPOEM) is efficient for the stabilization of liposomes in blood circulation.

Cationic liposomes modified with non-ionic surfactants as effective non-viral carrier for gene transfer

A defined change in formulation components affects the physical and chemical characteristics of cationic liposomes (CLs) carriers in many ways. Therefore, a great degree of control can be exercised over the structure by modifying the CLs with various materials, leading to new innovations for carrier improvement. In the present study, surface modifications of cationic liposomes with non-ionic surfactants—sorbitan monoesters serials (Span 85, 80, 40 and 20) were carried out for developing a new gene transfer carrier. Span modified cationic liposomes (Sp-CLs) were prepared by reverse phase evaporation method (RPV) and self-assemble complexes of antisense oligonucleotides/surfactant modifying cationic liposomes were prepared by auto-coacervation through electrostatic effect. Characterization of Sp-CLs and the self-assembled complex was performed by electron microscope, particle size, zeta potential, turbidity and agarose electrophoresis. Furthermore, in vitro cellular uptake experiment showed that Span plays a role in enhancing the cellular uptake of encapsulated oligonucleotides mediated by Sp-CLs by the endocytosis-dependent route. CLs modified with Span 40 significantly facilitated the cellular uptake by COS-7 cells and HeLa cells; also showed some positive effect on gene expression. That suggests it is a potential non-viral carrier for efficient gene transfer.

항암제를 함유한 키토산 코팅 리포솜과 DNA 복합체의 제조

To enhance therapeutic efficacy of anticancer treatment, combination therapies which administrate both chemotherapeutic agent and therapeutic DNA have been developed. Negatively charged liposomes containing chemotherapeutic agent were prepared and surface of the liposomes were modified with a polycationic polymer, chitosan. The green fluorescence protein expressing plasmid DNA (pcDNA-GFP) was conjugated with the modified liposomes and the transfection efficiency was inspected. The particle size and zeta potential of the liposomes containing chemotherapeutic agent were 120 nm and 0 mV, respectively. Incorporation of DPPA into liposomes resulted increase of the particle size up to 170 nm and change of zeta potential to -50 mV. Loading efficiency of chemotherapeutic agent, doxorubicin, in the liposomes was not dependent on the concentration of DPPA. After surface modification of liposomes with chitosan, the particle size increased to 220 nm and the surface charge was positive with a zeta potential of +30 mV. The optimal neutralization ratio of DNA/liposome complex by gel retardation assay and measuring fluorescence intensity by EtBr was 0.5-1.0 (v/v). The transfection of plasmid DNA complex into human cervix adenocarcinoma cells (HeLa) was monitored by fluorescence microscopy. The transfection efficiency of plasmid DNA mediated by the chitosan-modified liposome was better compared to the naked DNA.

Doxorubicin-encapsulated thermosensitive liposomes modified with poly( N-isopropylacrylamide- co-acrylamide): Drug release behavior and stability in the presence of serum

In the field of the temperature sensitive drug delivery systems, we studied on the surface modification of liposomes by using poly( N-isopropylacrylamide- co-acrylamide) (PNIPAM-AAM) and polyethyleneglycol (PEG) to increase the release of doxorubicin (DOX) from liposomes and prolong the stability of liposomes in the presence of serum. The release of DOX from the PNIPAM-AAM/PEG modified liposomes is enhanced around the transition temperature of the polymer. In addition, the stability of the PNIPAM-AAM/PEG modified liposomes in serum shows a high level comparing with polymer unmodified liposomes. These results suggest that the modification on the surface of liposomes with both PNIPAM-AAM and PEG enhances the drug release from liposomes and reduces the protein adsorption in serum.