Search Results (9)

Liposomes are intensively used as nanocarriers for biology, biochemistry, medicine, and in the cosmetics industry and their non-toxic and biocompatible nature makes these vesicles attractive systems for biomedical applications. Moreover, the conjugation of specific ligands to liposomes increases their cellular uptake and therapeutic efficiency. Considering these aspects, the aim of the present study was to obtain new formulations of cationic liposomes coated with dual-peptide functionalized carboxymethyl chitosan (CMCS) for the treatment of inner ear diseases. In order to achieve efficient active targeting and ensuring a high efficacy of the treatment, CMCS was functionalized with Tet1 peptide, to target specific ear cells, and TAT peptide, to ensure cellular penetration. Furthermore, dexamethasone phosphate was loaded as a model drug for the treatment of ear inflammation. The infrared spectroscopy confirmed the functionalization of CMCS with the two specific peptides. The mean diameter of the uncovered liposomes varied between 167 and 198 nm whereas the CMCS-coated liposomes ranged from 179 to 202 nm. TEM analysis showed the spherical shape and unilamellar structure of liposomes. The release efficiency of dexamethasone phosphate after 24 h from the uncoated liposomes was between 37 and 40% and it appeared that the coated liposomes modulated this release. The obtained results demonstrated that the liposomes are hemocompatible since, for a tested concentration of 100 µg/mL, the liposome suspension had a lysis of erythrocytes lower than 2.5% after 180 min of incubation. In addition, the peptide-functionalized CMCS-coated liposomes induced a non-significant effect on the viability of normal V79-4 cells after 48 h, at the highest doses. Values of 71.31% were recorded (CLCP-1), 77.28% (CLCP-2) and 74.36% (CLCP-3), correlated with cytotoxic effects of 28.69%, 22.72%, and 25.64%. Full article

Background/Objectives: Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery. Methods: Poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide (mPEG-b-p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined. Results: The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes. Conclusions: The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema. Full article

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy. Full article

AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer–ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a K_D in the order of nM. The aptamer-functionalized liposomes loaded with ligands C₈ and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C₈ and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C₈ shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments. Full article

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer–liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells. Full article

Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as −22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control. Full article

Liposomes have been one of the most exploited drug delivery systems in recent decades. However, their large-scale production with low batch-to-batch differences is a challenge for industry, which ultimately delays the clinical translation of new products. We have investigated the effects of formulation parameters on the colloidal and biopharmaceutical properties of liposomes generated with a thin-film hydration approach and microfluidic procedure. Dexamethasone hemisuccinate was remotely loaded into liposomes using a calcium acetate gradient. The liposomes produced by microfluidic techniques showed a unilamellar structure, while the liposomes produced by thin-film hydration were multilamellar. Under the same remote loading conditions, a higher loading capacity and efficiency were observed for the liposomes obtained by microfluidics, with low batch-to-batch differences. Both formulations released the drug for almost one month with the liposomes prepared by microfluidics showing a slightly higher drug release in the first two days. This behavior was ascribed to the different structure of the two liposome formulations. In vitro studies showed that both formulations are non-toxic, associate to human Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells, and efficiently reduce inflammation, with the liposomes obtained by the microfluidic technique slightly outperforming. The results demonstrated that the microfluidic technique offers advantages to generate liposomal formulations for drug-controlled release with an enhanced biopharmaceutical profile and with scalability. Full article

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch’s membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy. Full article

Endowing implants with antibacterial ability and osteogenic ability plays important roles in preventing post-operative bacterial contamination and facilitating integration between implants and osseous tissue, consequently reducing implant failure rates. In this study, we develop a facile and versatile strategy with dopamine as an auxiliary for construction of dexamethasone (Dex)/liposome porous coatings. In detail, the surfaces of sulfonated polyetheretherketone (SP) plates are coated with polydopamine firstly and then modified with graphene oxide (GO) and dexamethasone (Dex)-loaded liposome, which is verified by contact angle, X-ray photoelectron spectroscopy (XPS), attenuated total reflection infrared (ATR), and Raman spectra. The results of our study suggest that the GO and Dex are successfully coated on the samples’ surfaces. In vitro cell attachment, growth, differentiation, and apatite deposition tests all illustrate that the substrate coated with GO and Dex can significantly accelerate the proliferation and osteogenic differentiation of MC3T3 cells compared with the pristine sulfonated polyetheretherketone (PEEK). Additionally, it exhibits acceptable antibacterial activity against E. coli and S. aureus in vitro. Altogether, our results demonstrate that the modified GO- and Dex-loaded substrates are endowed with impressive biocompatibility and certain antibacterial qualities, making it possible for future application as a perspective implant material. Full article