Interaction of ionic compounds with multilamellar liposomes. An electrokinetic model

We have proposed a theoretical model of interaction of ionic compounds (ionic adsorbate or ionic drugs), with multilamellar-liposomes, by means of their electrokinetic property variation with the ionic compound concentration. In this work, we show the complete development of the model proposed. Its theoretical results have been analysed to study the influence on the zeta-potential value of the following: number of membranes, size, shear-plane situation, critical concentration of formation (ccf), and the ionic compound concentration which annuls the zeta-potential value of the multilamellar-liposomes formed.     

肽类树枝状大分子:自组装胶束及药物释放研究

本文以三代聚谷氨酸肽类树枝状分子(G3-Glu)为大分子引发剂,引发N-羧基-L-苯丙氨酸-环内酸酐(NCA-Phe)的开环聚合反应,制备聚谷氨酸树枝状大分子-聚苯丙氨酸嵌段共聚物.嵌段共聚物通过自组装形成以聚苯丙氨酸链段为核,聚谷氨酸树枝状大分子为壳的胶束.将抗肿瘤药物阿霉素负载到高分子胶束中,研究其药物释放性能及体外抗肿瘤效果.结果表明,共聚物胶束具有良好的生物相容性.载药胶束具有药物缓释效果,药物持续释放时间可达60h.载药胶束的体外抗肿瘤实验表明其对肝癌细胞HepG2具有很好的杀灭效果,共培养48h后对癌细胞的杀死率可高达75%.     

Polypeptide dendrimers: Self-assembly and drug delivery

Amphiphilic dendritic poly(glutamic acid)-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly(glutamic acid) as the macroinitiator in the ring-opening polymerization of NCA-Phe.The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly(glutamic acid) segments as shell.The biocompatibility of the micelles was studied.The release of the anticancer drug doxorubicin from the micelles was investigated in vitro.The results showed that the ...     

Fluorescent dendrimers with a peptide cathepsin B cleavage site for drug delivery applications

The synthesis of a multifunctionally equipped first generation (G1) dendrimer carrying a pentapeptide with a cathepsin[space]B cleavage site, chelating ligands for Pt2+-complexation, and a dansyl fluorescence marker is described and an investigation of its cellular uptake as well as intracellular localization by confocal fluorescence microscopy reported.     

Studies on pectin coating of liposomes for drug delivery

The present study investigated the surface coating of charged liposomes by three different types of pectin (LM, HM and amidated pectin) by particle size determinations and zeta potential measurements. The pectins and the pectin coated liposomes were visualized by atomic force microscopy. The adsorption of pectin onto positive liposomes yielded a reproducible increase in particle size and a shift of the zeta potential from positive to negative side for all three pectin types, whereas the adsorption of pectin onto negative liposomes did not render any significant changes probably due to electrostatic repulsion. The positive liposomes coated with HM-pectin gave the largest pectin coated particles with the least negative zeta potential, while the opposite was observed for the LM-pectin coated positive liposomes. Furthermore, results from dynamic light scattering revealed narrow size distributions, indicating that the degree of aggregation was low for the pectin coated liposomes. As liposomes are able to encapsulate drugs and pectin has been found to be mucoadhesive, these pectin coated liposomes may be potential drug delivery systems.     

Polymer-associated liposomes as a novel delivery system for cyclodextrin-bound drugs

It is known that cyclodextrins (CDs) extract lipid components from bilayer of liposomes. This could undermine the potential benefits of liposomes as drug carriers. In this study, we demonstrated that PC-Chol liposomes with various CDs or rhapontin (Rh)-hydroxypropyl betaCD (HPbetaCD) complexes could be stabilized by association with the amphiphilic polyelectrolyte, poly(methacrylic acid-co-stearyl methacrylate). Based on the results of differential scanning calorimetry, photocorrelation spectroscopy and transmission electron microscopy, the polymer-associated liposomes had the same vesicular form as liposome with clear boundaries and retained structural integrity for at least 1 month. In addition, the polymer-associated structure was unaffected by the type of CD, the composition and concentration of lipid components, and the concentration of the Rh-HPbetaCD complex. This contrasted with PC-Chol liposomes, whose structure was dependent on these factors. Using structurally different polymer-associated liposomes and PC-Chol liposomes containing the Rh-HPbetaCD complex, we also showed that the stability of vesicles could influence the skin permeability of CD-drug complexes.     

Polyamidoamine dendrimers surface-engineered with biomimetic phosphorylcholine as potential drug delivery carriers

Biomimetic acryloyloxyethyl phosphorylcholine (APC) was used to react with generation 5 poly(amido amine) (PAMAM) dendrimers (G5) via the Michael addition reaction between primary amino group of PAMAM dendrimers and acrylic functional group of APC. FTIR and (1)H NMR confirmed the success of surface modification of G5. The primary amino and phosphorylcholine (PC) group numbers of the surface engineered PAMAM dendrimers (G5-PC) were calculated to be 56 and 50 via (1)H NMR and potentiometric titration. Cell viability and cell morphology studies indicated that biomimetic phosphorylcholine surface engineering successfully lowered the cytotoxicity of G5 PAMAM dendrimers. The hydrophobic interior of G5-PC was used to incorporate anti-cancer drug Adriamycin (ADR) and the G5-PC showed sustained releasing behavior for ADR. Cell morphology and viability tests indicated that the drug-loaded G5-PC conjugate could effectively enter the cancer cells and inhibit the growth of cancer cells. Biomimetic phosphorylcholine surface engineered PAMAM dendrimers with lowered cytotoxicity and high cellular penetrating ability showed great potential for the biomedical applications as nanocarrier system.     

Design and synthesis of novel amphiphilic Janus dendrimers for bone-targeted drug delivery

In this paper, we synthesized a range of amphiphilic Janus dendrimers, which consisted of acidic amino acid and naproxen molecules as the peripheral groups, as novel potential bone-targeting dendritic drug delivery. These dendrimers take advantage of a dendritic display to carry multiple drug molecules and targeting moieties simultaneously. All of the dendrimers exhibited more than 80% binding rates to hydroxyapatite (HAP), especially the [G₂]-dendrimers (2a and 2b) showed dramatic binding rates (>95%). Moreover, the solubility of naproxen was remarkably enhanced by the dendritic drug delivery system, especially the naproxen concentration of 2b achieved 5.37 mg/ml, which is more than 28-fold over that of native drug. Furthermore, cell viability studies showed that all the dendrimers exhibited no significant cytotoxicity against HEK293 cells. These results provided an effective entry to the development of new bone-targeting drugs.     

Hydrogel design strategies for drug delivery

Hydrogels are water-swollen three-dimensional networks made of polymers, proteins, small molecules or colloids. They constitute a versatile platform for drug delivery because of their capacity to encapsulate and protect drugs and provide sustained and/or remotely programmable spatial and temporal release and have thus generated a substantial amount of research for the delivery of either small active compounds or biopharmaceuticals. This article discusses the features that make hydrogels attractive as matrices for delivery and reviews a range of designs, focussing on studies from recent years, in particular: ‘smart’ hydrogels (responding to temperature, light, magnetic fields, ultrasounds or combined stimuli); recent technologies: 3D printing and microneedles; and closes by discussing polymer-free drug delivery systems: peptides, small molecules and colloids.     

Interaction of water-soluble polypyridylphenylene dendrimers with a polymethacrylate anion

Cationic water-soluble dendrimers have been prepared by the alkylation of pyridyl groups in polypyridylphenylene dendrimers of the first four generations, and their interaction with a polymethacrylate anion has been studied. The stability of polyelectrolyte complexes in aqueoussaline solutions has been studied by fluorimetric titration with the use of the pyrenyl-tagged polyanion, and it has been shown that the stability of these complexes significantly increases with the dendrimer generation number and the content of hydrophobic phenylene groups. Based on sedimentation analysis and turbidimetric titration, it is inferred that a significant part of charged groups of dendrimers are inaccessible to interaction with the polyanion and that water-soluble nonstoichiometric polyelectrolyte complexes develop in mixtures of higher generation dendrimers. Modeling results of this study may be useful for designing efficient cationic dendrimer carriers of genetic material and hydrophobic physiologically active compounds.     

Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

Paclitaxel(PTX) is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers, whereas its efficacy is always impeded by poor solubility. Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’ tolerance owing to excellent biocompatibility and biodegradability. However, poor compatibility between PTX and liposomes compromises the stability, drug loading and anti-tumor capacity of lipo...     

Enhanced drug transport from unilamellar to multilamellar liposomes induced by molecular recognition of their lipid membranes

Unilamellar PC-based liposomes bearing a recognizable moiety were loaded either with the hydrophilic drug doxorubicin (DXR) or with the hydrophobic drug tamoxiphen (TMX) and allowed to interact with multilamellar PC-based liposomes bearing complementary recognizable groups. It has been established that, due to molecular recognition of these complementary liposomes, effective and fast transport of the drugs occurs from unilamellar to multilamellar liposomes. The transport of TMX is more effective compared to that of DXR. This behavior was observed for both PEGylated and non-PEGylated unilamellar liposomes, and it was attributed to the different sites of solubilization of the drugs in the unilamellar liposomes. PEGylation reduces the transport of both drugs since it inhibits to some extent the molecular recognition effectiveness of the complementary moieties.     

Pyridine-Ag20 cluster: a model system for studying surface-enhanced Raman scattering

This work presents a detailed analysis of enhanced Raman scattering of the pyridine-Ag(20) model system using time-dependent density functional theory. A consistent treatment of both the chemical and electromagnetic enhancements (EM) is achieved by employing a recently developed approach based on a short-time approximation for the Raman cross section. A strong dependence of the absolute and relative intensities on the binding site and excitation wavelength is found. The analysis of the Raman scattering cross sections shows the importance of different contributions to the enhancements, including static chemical enhancements (factor of 10), charge-transfer enhancements (10(3)), and EM enhancements (10(5)). The largest enhancement found (10(5)-10(6)) is due to the EM mechanism, with a small contribution from the chemical interaction. This suggests that the enhanced Raman scattering due to atomic clusters is comparable to findings on single nanoparticles. A combination of information about the vibrational motion and the local chemical environment provides a simple picture of why certain normal modes are enhanced more than others.     

Interaction of ampholyte dendrimers with linear polyelectrolytes

The interaction of ampholyte propylenimine dendrimers containing peripheral carboxyl groups and inner tertiary amino groups with linear polyelectrolytes has been studied. Both in acidic and alkaline media up to pH ～ pI, dendritic polyampholytes can form interpolyelectrolyte complexes with flexible linear polyanions and polycations. A variation in the composition of complexes with a change in pH is associated with the formation of intramolecular zwitterion pairs in a dendrimer molecule. The ability of interpolyelectrolyte complexes to dissolve in water is shown to be determined by the degree of dissociation of ionogenic groups of the dendrimer not directly involved in the formation of interpolyelectrolyte salt bonds stabilizing the complex. It has been demonstrated that the territorial separation of carboxyl and tertiary amino groups in the polyampholyte dendrimers is reflected in different structures of interpolyelectrolyte complexes formed by dendrimers with oppositely charged linear polyions.     

Rational design of nanocarriers for mitochondria-targeted drug delivery

Well-developed mitochondria-targeted nanocarriers for function regulation are highly desirable. Numerous studies have been conducted on the treatment of mitochondria-related diseases; however, further improvements are required to develop more effective drug delivery methods. Herein, we comprehensively introduce recent developments progress in rational design of mitochondria-targeted nanocarriers, and discuss the different strategies of available nanocarriers for targeting mitochondria. We also highlight the advantages and disadvantages of various carrier systems that are currently in use. Finally, perspective on new generation for mitochondria-targeted delivery systems in the emerging area of drug-based therapeutics is also discussed.     

Multiparticulate chitosan-dispersed system for drug delivery

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.     

Metallocorrole dendrimers: sensitive corrole-chromium(V)-nitride spin probes for studying the solution structure of dendrimers

The corrole-chromium(V)-nitrido moiety is introduced as a uniquely sensitive EPR spin probe. We describe a series of corrole-centered poly(amidoamine) (PAMAM) dendrimers and the selective incorporation of the chromium(V)-nitrido moiety. The chromium-corrole cores are reactive toward both neutral and charged reagents, and the accessibility of the dendrimer cores enables easy manipulation of the spin probe. The spin probe reveals a pronounced solvent dependence of the solution-phase structure of the dendrimers.     

Chitosan modified with terephthaloyl diazide as a drug delivery system

Russian Chemical Bulletin - pH- and thermo-sensitive hydrogels based on chitosan cross-linked with terephthaloyl diazide were synthesized. A new formulation of the polysaccharide modified with...     

A pharmacokinetic model for ocular drug delivery

A pharmacokinetic model of ocular drug delivery has been developed for describing the elimination and distribution of ocular drugs in the eye. The model, based on Fick's second law of diffusion, assumes a modified cylindrical eye with three pathways for drug transport across the surface of the eye: the anterior aqueous chamber, the posterior aqueous chamber and the retina/choroids/scleral membrane covering the vitreous body. The model parameters such as the diffusion coefficient and the partition coefficient in various eye tissues can be evaluated from the in vitro membrane penetration experiments using a side-by-side diffusion cell system. The diffusion coefficient for a drug is also predicted by taking account of the effect of the molecular weight of model compounds. The present ocular pharmacokinetic model, which can predict the local concentration distribution in the eye, has well described the in vivo concentration profile in the various eye tissues, the lens, the aqueous humor and the vitreous body, following not only topical eye drop instillation but systemic administration as well. The present model also simulates the effects of binding and metabolism in the eye as well as the individual difference in ocular functions and structure such as cataract surgery and vitreous fluidity on the distribution and elimination of drug molecules in the eye.