Stability of SUV liposomes in the presence of cholate salts and pancreatic lipases: effect of lipid composition.

The effect of bile salts (sodium cholate and sodium taurocholate), and pancreatic lipases on the structural integrity of SUV liposomes of different lipid compositions was studied. Liposomal membrane integrity was judged by bile salt or pancreatin-induced release of vesicle encapsulated 5,6-carboxyfluorescein, and vesicle size distribution before and after incubations. Bile salt concentration was 10 mM, while a saturated solution of pancreatin (mixed with equal volume of liposomes) was utilized. Results agree with earlier studies, demonstrating the instability of liposomes composed of lipids with low transition temperatures (PC and DMPC) in presence of cholates. Addition of cholesterol (1:1 lipid:chol molar ratio) does not substantially increase the encapsulated molecule retention. Nevertheless, liposomes composed of lipids with high transition temperatures (DPPC, DSPC and SM), retain significantly higher amounts of encapsulated material, under all conditions studied. Furthermore, the vesicles formed by mixing cholesterol with these lipids will possibly be sufficiently stable in the gastrointestinal tract for long periods of time. Sizing results reveal that in most cases release of encapsulated molecules is mainly caused by their leakage through holes formed on the lipid bilayer. However, in stearylamine containing DPPC and DSPC vesicles, the cholate-induced drastic decrease in vesicle size suggests total liposome disruption as the possible mechanism of encapsulated material immediate release.     

Dexamethasone incorporating liposomes: effect of lipid composition on drug trapping efficiency and vesicle stability

Effect of lipid composition on encapsulation and stability of dexamethasone (DXM) incorporating multilamellar vesicles (MLV) is studied. MLVs composed of phosphatidylcholine (PC) or distearoyl-glycero-PC (DSPC), with or without cholesterol (Chol), are prepared and the release of DXM during vesicle incubation in buffer or plasma proteins is evaluated. Incorporation of DXM is slightly higher in DSPC liposomes compared with PC, whereas the drug is displaced from liposomes, as the Chol content of liposome membranes increases. Plain lipid and Chol-containing liposomes lose similar fractions of vesicle-incorporated DXM during incubation in buffer or serum, whereas DXM release kinetics are similar (for each liposome type studied), implying that drug release is due mainly to dilution of liposome dispersions that leads to repartitioning of DXM.     

Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy

pH-responsive polymers render liposomes pH-sensitive and facilitate the intracellular release of encapsulated payload by fusing with endovascular membranes under mildly acidic conditions found inside cellular endosomes. The present study reports the use of high-molecular weight poly(styrene-co-maleic acid) (SMA), which exhibits conformational transition from a charged extended structure to an uncharged globule below its pK(1) value, to confer pH-sensitive property to liposomes. The changes in the co-polymer chain conformation resulted in destabilization of the liposomes at mildly acidic pH due to vesicle fusion and/or channel formation within the membrane bilayer, and ultimately led to the release of the encapsulated cargo. The vesicles preserved their pH-sensitivity and stability in serum unlike other polymer-based liposomes and exhibited no hemolytic activity at physiological pH. The lysis of RBCs at endosomal pH due to SMA-based liposome-induced alterations in the bilayer organization leading to spherocyte formation indicated the potential of these vesicles to mediate cytosolic delivery of bio-active molecules through endosome destabilization. The SMA-loaded liposomes exhibiting excellent cytocompatibility, efficiently delivered chemotherapeutic agent 5-Fluorouracil (5-FU) within colon cancer cells HT-29 in comparison to neat liposomes. This caused increased cellular-availability of the drug, which resulted in enhanced apoptosis and highlighted the clinical potential of SMA-based vesicles.     

Liposomes encapsulating prednisolone and prednisolone-cyclodextrin complexes: comparison of membrane integrity and drug release.

Inclusion complexes of prednisolone (PR) with beta-cyclodextrin (beta-CD) and hydropropyl-beta-cyclodextrin (HPbeta-CD) were formed by the solvation method, and were characterized by DSC, X-ray diffractometry and FT-IR spectroscopy. PC liposomes incorporating PR as plain drug or inclusion complex were prepared using the dehydration-rehydration method and drug entrapment as well as drug release were estimated for all liposome types prepared. The highest PR entrapment value (80% of the starting material) was achieved for PC/Chol liposomes when the HPbeta-CD-PR (2:1, mol/mol) complex was entrapped. The leakage of vesicle encapsulated 5,6-carboxyfluorescein (CF) was used as a measure of the vesicle membrane integrity. As judged from our experimental results liposomes which encapsulate beta-CD-PR complexes are significantly less stable (when their membrane integrity is considered) compared to liposomes of identical lipid compositions which incorporate plain drug or even (in some cases) non-drug incorporating liposomes, which were prepared and studied for comparison. Interestingly, liposomes which encapsulate HPbeta-CD-PR complexes, have very low initial CF latency values, indicating that the leakage of CF is a process of very high initial velocity. Interactions between lipid and cyclodextrin molecules may be possibly resulting in rapid reorganization of the lipid membrane with simultaneous fast release of CF molecules. The release of PR from liposomes was highest when the drug was entrapped in the form of a complex with beta-CD. Nevertheless, the very high entrapment ability of PR in the form of HPbeta-CD-PR complexes in comparison to plain drug is a indubitable advantage of this approach.     

Effect of preparation method and cholesterol on drug encapsulation studies by phospholipid liposomes

Unilamellar liposomes, prepared from synthetic lipid mixture of DMPC and DMPG either by sonication or extrusion, were used to entrap water soluble and water insoluble molecules to investigate the efficacy of encapsulation by different liposome preparation methods. In the case of entrapment of hydrophilic protein cytochrome-C, the solutions were subjected to a series of ultrafiltration steps to eliminate any free protein outside the vesicles. It was observed that the protein could be encapsulated by the vesicles only if cholesterol was present in the bilayer. The release of cytochrome-C was observed spectrophotometrically upon vesicle-breakdown. The amount of protein encapsulated depended on the method of preparation and was found to be 10 times greater in extruded liposomes compared to those produced by sonication. Hydrophobic Vitamin E, on the other hand, could be encapsulated in the liposome bilayer, independently of the presence of cholesterol and the method of preparation. These fundamental results can be used to develop more efficient drug encapsulations and to have better understanding about their release.     

Microencapsulated liposomes in controlled drug delivery: strategies to modulate drug release and eliminate the burst effect

The release of fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from alginate-microencapsulated liposomes was studied to evaluate the properties of this system for controlled drug delivery. Liposomes composed of phosphatidylcholine (PC) and cholesterol (Chol) (molar ratio 7:3) and of PC, phosphatidylglycerol (PG), and cholesterol (6:1:3) were encapsulated in alginate (Alg) crosslinked with Ca(2+) (Ca-Alg), Al(3+) (Al-Alg), and Ba(2+) (Ba-Alg). Capsules were coated with poly(l-ornithine) followed by a final alginate coat. A rapid initial burst of protein release was observed from liposomes encapsulated in Ca-Alg and Al-Alg. No burst was observed when liposomes were encapsulated in Ba-Alg, indicating that the crosslinking ions could significantly affect the release of entrapped protein. Also, the release from encapsulated liposomes varied significantly with liposome composition, especially with Ca-Alg as observed with encapsulation of PC, dioleoylphosphatidylcholine (DOPC), and DOPC/Chol liposomes. Cholesterol increased the leakiness of the liposomes after encapsulation. In all cases, the release from microencapsulated liposomes was much faster than that from free liposomes suggesting an interaction between the liposomes and the alginate. Differential scanning calorimetry supports the hypothesis that alginate was inserted into the lipid bilayer resulting in a rapid release of protein from microencapsulated liposomes. Moreover, it was observed that the degree of interaction between liposomes and alginate varied with liposome composition.     

Sterile filtration of liposomes: Retention of encapsulated carboxyfluorescein

Multilamellar vesicles incorporating carboxyfluorescein (CF) were calibrated through polycarbonate membranes of 0.1, 0.2 or 0.4 μm pore size. After removal of unencapsulated material, the vesicles were passed through 0.2 μm sterilizing filters constituted of polycarbonate, cellulose acetate or polyvinylidene fluorure (PVDF). The liposomes were readily filtered without significant change in the vesicle size and loss of phospholipids. The leakage of encapsulated material was only slight, lower than 5% in all cases, except for vesicles of 300 nm sterilized through polycarbonate membranes of 0.2 μm pore size. However, the same preparation was easily passed through 0.2 μm acetate cellulose membranes without significant leakage of the incorporated dye. In spite of the small size of the liposomes, trapping efficiencies up to 33% were achieved, depending on the vesicle mean diameter, lipid concentration, bilayer composition and inclusion of freeze-thawing cycles.     

Stability of Liposomes on Storage: Freeze Dried,Frozen or as an Aqueous Dispersion

For various types of liposomes carboxyfluorescein (CF) latency and physical stability on storage were investigated. Three regimens were compared: storage at 4–6°C in an iso-osmotic aqueous buffer, freezing of the dispersions at –5 or –30°C, or freeze drying of the dispersions. Reverse phase evaporation vesicles (REV) were used with mean diameters between 0.2 and 0.3 µm. Liposomes consisted of egg phosphatidylcholine (PC) and phophatidylserine (PS) without or with cholesterol (chol) (9/1 and 10/1/4, respectively) or of distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidylglycerol (DPPG) without or with chol (10/l/[5]). PC/PS liposome dispersions lost 25% of the entrapped CF within 10 days. The leakage rate decreased with the inclusion of cholesterol in the bilayer. Both after a freezing/thawing cycle and after freeze-drying no acceptable CF latency could be obtained. The cryoprotectants that were tested failed to raise CF latency significantly. However, the physical integrity of the liposomes could be maintained by proper choice of the cryoprotectant. When stored at 4–6°C, DSPC/DPPG/(chol) dispersions were stable for at least 6 months. Upon freezing/thawing less than 10 % CF was lost. Freeze drying without cryoprotectants reduced CF latency dramatically on rehydration. The physical structure was maintained and maximum latencies of 70 % could be obtained with the use of lactose as a cryoprotectant.     

Equilibrium uptake of D-glucose by osmotically stressed unilamellar phospholipid vesicles

The assumptions inherent in the use of osmotic manipulation to determine the extent of solute binding to brush border membrane vesicles (the ideal osmotic responsiveness of the vesicles and the independence of solute binding from the incubation medium osmotic pressure) were examined in a model system (large unilamellar lipid vesicles). The equilibrium uptake of D-glucose by unilamellar vesicles composed of egg lecithin (PC), phosphatidic acid (PA), and cholesterol (Chol) was measured as a function of the osmotic concentration of the incubation medium. The variation of the encapsulated aqueous volume of PC:PA and PC:PA:Chol vesicles with the osmotic stress was directly determined by a fluorescence self-quenching technique. Encapsulated volume changes of both PC:PA and PC:PA:Chol vesicles were found to be resistant to the osmotic stress, exhibiting positive deviations from ideal behavior. Equilibrium uptake experiments with these vesicles showed that glucose was taken up in excess of that amount predicted on the basis of the encapsulated volume when the vesicles were subjected to osmotic stress less than 0.25 osmol/kg. At osmotic stresses greater than 0.75 osmol/kg, equilibrium uptake could be predicted solely on the basis of the encapsulated volume. These results, based on a model vesicle system, strongly suggest that osmotic manipulation may be an inappropriate method to assess the extent of solute binding to natural membrane vesicle preparations, such as brush border membrane vesicles, without more direct evidence.     

Radiopaque liposomes: effect of formulation conditions on encapsulation efficiency

Liposomes containing sodium ioxitalamate were prepared by sonication. Suitable amounts of purified soybean phosphatidylcholine and cholesterol were used at various molar ratios. Stearylamine or dicetylphosphate were added to this lipid composition when charged liposomes were required. After sonication and removal of unencapsulated solute, this manufacturing process yielded small multilamellar vesicles as confirmed by electron microscopy. These liposomes did not exhibit a narrow range of size distribution; the mean particle size varied from 135 to 145 nm. With respect to the efficiency of encapsulation, two parameters were distinguishable: the volume of encapsulated aqueous space per unit of lipid weight and the percentage of the contrast agent added that became encapsulated in the liposomes. Investigation of the preparative parameters revealed that increased molar ratios of cholesterol yielded higher aqueous volume and iodine contents in the liposomes, which were attributed to a reduction of the liposome permeability to the contrast agent. However, the inclusion of cholesterol into the bilayer liposomal membrane was limited, probably by solubility restrictions. Negatively and positively charged liposomes had higher rates of encapsulation than did neutral liposomes. This result was expected since efficient encapsulation of polar compounds requires formation of large aqueous spaces within the vesicles per mole of lipids. Increase of the lipid fractions at a constant, reduced the aqueous volume entrapped per millimole of lipid and, consequently, the iodine content in the liposomes. However, an increase in the initial sodium ioxitalamate concentration diminished the aqueous volume entrapped in the liposomes but increased the iodine content.     

Dexamethasone Incorporating Liposomes: Effect of Lipid Composition on Drug Trapping Efficiency and Vesicle Stability

Effect of lipid composition on encapsulation and stability of dexamethasone (DXM) incorporating multilamellar vesicles (MLV) is studied. MLVs composed of phosphatidylcholine (PC) or distearoyl-glycero-PC (DSPC), with or without cholesterol (Chol), are prepared and the release of DXM during vesicle incubation in buffer or plasma proteins is evaluated. Incorporation of DXM is slightly higher in DSPC liposomes compared with PC, whereas the drug is displaced from liposomes, as the Chol content of liposome membranes increases. Plain lipid and Chol-containing liposomes lose similar fractions of vesicle-incorporated DXM during incubation in buffer or serum, whereas DXM release kinetics are similar (for each liposome type studied), implying that drug release is due mainly to dilution of liposome dispersions that leads to repartitioning of DXM.     

Niosomes as carriers for tretinoin. I. Preparation and properties

Tretinoin-loaded niosomes were prepared from polyoxyethylene (4) lauryl ether, sorbitan esters and a commercial mixture of octyl/decyl polyglucosides, in the presence of cholesterol and dicetyl phosphate. Liposomes made of hydrogenated and non-hydrogenated phosphatidylcholine were also prepared as a comparison reference. A study was made of the influence of vesicle composition and preparation method on the vesicle structure (MLV, LUV, SUV), size distribution, entrapment efficiency and in vitro release of incorporated tretinoin. Results showed that in the presence of cholesterol all the amphiphiles used were able to form stable vesicle dispersions with or without tretinoin. Vesicle sizes were dependent on the preparation method, bilayer composition and drug load. Multilamellar (MLV) vesicles were larger than extruded (LUV) and sonicated (SUV) vesicles while drug-loaded vesicles were generally smaller than empty ones. Entrapment efficiencies of tretinoin were always very high especially for multilamellar (91-99%) and extruded (88-98%) vesicles. The in vitro release of tretinoin from the prepared vesicular formulations was studied using the vertical Franz diffusion cells. The rate of drug release through a Silastic membrane from a liposomal and niosomal tretinoin dispersion was generally faster than from a tretinoin solution. Release data showed that tretinoin delivery is mainly affected by the vesicular structure and that tretinoin delivery increased from MLVs to LUVs to SUVs.     

Polymeric Chitosan-based Vesicles for Drug Delivery

A simple carbohydrate polymer glycol chitosan (degree of polymerization 800 approx.) has been investigated for its ability to form polymeric vesicle drug carriers. The attachment of hydrophobic groups to glycol chitosan should yield an amphiphilic polymer capable of self-assembly into vesicles. Chitosan is used because the membrane-penetration enhancement of chitosan polymers offers the possibility of fabricating a drug delivery system suitable for the oral and intranasal administration of gut-labile molecules. Glycol chitosan modified by attachment of a strategic number of fatty acid pendant groups (11–16mol%) assembles into unilamellar polymeric vesicles in the presence of cholesterol. These polymeric vesicles are found to be biocompatible and haemocompatible and capable of entrapping water-soluble drugs. By use of an ammonium sulphate gradient bleomycin (MW 1400), for example, can be efficiently loaded on to these polymeric vesicles to yield a bleomycin-to-polymer ratio of 0.5 units mg^?1. Previously polymers were thought to assemble into vesicles only if the polymer backbone was separated from the membrane-forming amphiphile by a hydrophilic side-arm spacer. The hydrophilic spacer was thought to be necessary to decouple the random motion of the polymer backbone from the ordered amphiphiles that make up the vesicle membrane. However, stable polymeric vesicles for use in drug delivery have been prepared from a modified carbohydrate polymer, palmitoyl glycol chitosan, without this specific architecture. These polymeric vesicles efficiently entrap water-soluble drugs.     

Nebulization of Liposomes. I. Effects of Lipid Composition

A series of multilamellar liposome dispersions was prepared from lipids of soy phosphatidylcholine or hydrogenated soy phosphatidylcholine containing from 0 to 30 mol% of either cholesterol, steary-lamine, or dipalmitoyl phosphatidylglycerol. The liposome dispersions were aerosolized with a Collison nebulizer for 80 min at an output flow rate of 4.7 liters of air/min. The effects of nebulization on the vesicles were determined by monitoring the release of encapsulated 5,6-carboxyfluorescein (CF) from dispersions containing 200 µg of total CF, of which 93.1 ± 2.4% (N = 18) was initially encapsulated. In all experiments CF was released from the liposomes while being aerosolized, and this ranged from a mean of 12.7 ± 3.8 to 60.9 ± 1.9% of the encapsulated CF, depending upon the lipid composition. The lipid concentration in the dispersions did not affect the rate or percentage release of CF over a range of 0.5 to 50 mg per nebulized dispersion. If liposomes are to be used as drug carriers in an inhalation aerosol a lipid composition should be employed which will minimize the release of encapsulated drug caused by nebulization.     

Doxorubicin-loaded lipid-quantum dot hybrids: surface topography and release properties

A few studies have attempted to combine the physicochemical versatility offered by the liposome structure with the superior optical characteristics of quantum dots (QD) for the construction of multifunctional nanoparticles. We are reporting the construction of drug-loaded liposome-QD hybrid vesicles (L-QD) by incorporating TOPO-capped, CdSe/ZnS QD into the two types of lipid bilayers: the ‘rigid’ disteroylphosphatidylcholine (DSPC:Chol:DSPE-PEG₂₀₀₀) and a fluid-phase bilayer of egg PC (EPC:Chol:DSPE-PEG₂₀₀₀). Structural characterization of L-QD hybrid vesicles using atomic force microscopy (AFM) revealed that the incorporation of QD took place by hydrophobic self-association within the membranes. The encapsulation of hydrophilic small molecules in the internal aqueous phase of the L-QD hybrids showed different degrees of carboxyfluorescein (CF) release in buffer and serum, depending on the type of lipid used. The presence of QD in the lipid bilayer increased the CF release from EPC fluid bilayer. On the other hand, (DSPC) L-QD hybrids showed a higher stability under the same conditions with minimal CF leakage. Furthermore, (DSPC) L-QD hybrids showed a stable mean diameter up to three weeks stored at 4 °C, 25 °C, and 40 °C, determined by photo correlation spectroscopy (PCS) analysis. Finally, doxorubicin (Dox) was loaded into L-QD hybrids using the osmotic gradient technique and with at least 97% loading efficiency. The fluorescence spectrum of Dox was simultaneously detected with that of green-emitting QD that indicated the coexistence of QD and Dox in a single vesicle system. In conclusion, the drug-loaded L-QD-Dox hybrid vesicles presented here constitute a promising multifunctional delivery vector capable of transporting combinations of therapeutic and diagnostic modalities.     

脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响

目的研究不同处方组成和制备方法对阿昔洛韦棕榈酸酯脂质体在4℃和25℃分别贮存90 d和180 d后的稳定性的影响。方法用卵磷脂(PC)/胆固醇(CH)/磷脂酰丝氨酸(PS),卵磷脂(PC)/胆固醇(CH)/硬脂酰胺(SA),卵磷脂(PC)/胆固醇(CH)/胆固醇硫酸酯(CS),神经酰胺(CM)/胆固醇(CH)/棕榈酸(PA)/胆固醇硫酸酯(CS),以薄膜分散法、逆向蒸发法和去水化/水化法,分别制备多室脂质体(MLV)、大单室脂质体(LUV)、去水化/水化脂质体(DRV),以平均粒径、渗漏率、pH值和Zeta电位4个指标考察不同贮存条件下脂质体的稳定性。结果脂质体稳定性顺序依次为,对不同脂质体处方:PC/CH/CS>CM/CH/PA/CS>PC/CH/PS>PC/CH/SA;对不同制备方法:LUV优于MLV和DRV;4℃时脂质体的稳定性优于25℃时的脂质体。结论脂质体的稳定性与制剂处方和制备方法密切相关。     

Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells

The over-expression of P-glycoprotein (P-gp) has been associated with the development of multidrug resistance (MDR) in cancer cells. In this study, we examined whether transferrin receptor (Tf-R) targeted liposomes can efficiently deliver encapsulated doxorubicin (DXR) into MDR cells (SBC-3/ADM) via Tf-R-mediated endocytosis thus overcoming MDR by by-passing P-gp-mediated drug efflux. We prepared four types of liposome, i.e. untargeted and Tf-R-targeted, made of either egg-PC/cholesterol or hydrogenated egg PC/cholesterol. Only with the targeted EPC-liposome we achieved significant delivery of encapsulated DXR and increased cytotoxicity of encapsulated DXR on the MDR cells (3.5-fold higher than free DXR). Confocal microscopy and an intracellular drug-accumulation assay indicated that the targeted liposomes efficiently delivered DXR into cells where it readily accumulated in the nucleus, in both drug-sensitive and MDR cells. These findings suggest that the targeted liposomes are rapidly internalized via Tf-R-mediated endocytosis followed by release of their contents into the cytoplasm. The rapid internalization and content release, most likely facilitated by the higher fluidity of the EPC-based liposomes, may explain why only targeted EPC-liposomes were able to prevent drug efflux by P-gp and to consequently circumvent MDR. Our results indicate that in order to achieve MDR circumvention by means of liposomal encapsulation of DXR the liposomes not only need to be targeted, but also to have the proper physicochemical properties for adequate release of the drug. Furthermore, these in vitro results suggest that Tf-R targeted EPC-liposomes are a potentially useful drug delivery system to circumvent P-gp-mediated MDR of tumors.     

Incorporation of alphaxalone into different types of liposomes

Abstract— The poor solubility of steroid anaesthetics in water has been a serious drawback in the development of clinically acceptable intravenous formulations. The use of Cremophor EL to solubilize steroids such as alphaxalone led to unacceptable hypersensitivity reactions and consequent withdrawal of this anaesthetic. In principle, liposomes can act as a safe solvent for the intravenous administration of alphaxalone. We report the incorporation of [¹⁴C]acetylated alphaxalone in both multilamellar vesicles and stable plurilamellar vesicles prepared from a range of amphiphiles including synthetic polyhydroxyl lipids. For both types of preparations, addition of cholesterol to phosphatidylcholine-based lipids caused an increase in encapsulation efficiency. Maximum encapsulation was achieved with the stable plurilamellar vesicle preparation of 1-stearyl-2-myristylglycerate-3, N-methylglucamine: cholesterol: egg phosphatidylcholine (78%). The rate of efflux of this anaesthetic from a range of liposomes was measured in serum. The highest rate (85% after 30 min) was observed with an equimolar egg phosphatidylcholine: cholesterol stable plurilamellar vesicle preparation. From these studies it can be concluded that liposomes offer a suitable alternative for intravenous delivery of steroidal anaesthetics.     

Targeted delivery of an anti-cancer agent via steroid coupled liposomes

In the present investigation, testosterone (T) was evaluated as a targeting ligand to direct the site-specific delivery of 5-Fluorouracil (5-FU) bearing liposomes to the androgen receptor (ARs) positive tumors and other organs like prostate, brain, and testis. The testosterone was conjugated with the distearoyl phosphatidyl ethanolamine (DSPE) and then this lipid conjugate, Testosterone-DSPE (T-DSPE) was used as one of the components of the liposome. The liposomes were prepared by cast film method using T-DSPE, egg PC, and cholesterol. Further these liposomes were characterized for vesicle shape, average size, polydispersity index, drug entrapment, and in vitro drug release. It was observed that the prepared liposomes were spherical in shape with an average size of 232?±?21?nm and 0.181?±?0.064 polydispersity index. The in vitro drug release study showed 79.50?±?2.81 percent drug release in 24?h. In vivo performance of the developed liposomes was evaluated using organ distribution study in male albino rats. Moreover the fluorescent microscopy was also performed using 6-Carboxyfluorescein (6-CF) as a fluorescent marker. The organ distribution and fluorescent uptake studies confirm that T-DSPE coupled liposomes were effectively taken up by various ARs expressing tissues. Thus, it may be concluded that the testosterone may be used as an effective ligand for the site-specific delivery of anti-cancer agents to various ARs positive carcinomas.     

Creating Functional Vesicle Assemblies from Vesicles and Nanoparticles

Vesicles (liposomes) have been shown to be excellent vehicles for drug delivery, yet assemblies of vesicles (vesicle aggregates) have been used infrequently in this context. However vesicle assemblies have useful properties not available to individual vesicles; their size can cause localisation in specific tissues and they can incorporate more functionality than is possible with individual vesicles. This article reviews progress on controlling the properties of vesicle assemblies in vitro, applications of vesicle assemblies in vivo, and our recent creation of magnetic nanoparticle–vesicle assemblies. The latter assemblies contain vesicles crosslinked by coated Fe₃O₄ nanoparticles and this inclusion of magnetic functionality makes them magnetically responsive, potentially allowing magnetically-induced contents release. This article describes further studies on the in vitro formation of these magnetic nanoparticle–vesicle assemblies, including the effect of changing magnetic nanoparticle concentration, pH, adhesive lipid structure and bilayer composition. These investigations have led to the development of thermally-sensitive magnetic nanoparticle–vesicle assemblies that release encapsulated methotrexate on warming.