Liposomal Nanohybrid Cerasomes Research Articles

Ultrasound-Controlled Delivery of Growth Factor-Loaded Cerasomes Combined with Polycaprolactone Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells for Biomimetic Tendon-to-Bone Interface Engineering.

Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFβ1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.

LIPOSOMAL HYBRID SILICON - ORGANIC MEANS OF DELIVERY OF MEDICINAL PREPARATIONS

Nowadays, chemotherapy is an important mean for cancer treatment. Despite many benefits, patients receiving anticancer drugs often suffer unfavorable side effects due to the non-specific toxicity of anticancer drugs. Most anticancer drugs can kill cancer cells with non-selective killing of the normal human cells, which brings great pains to patients. One of the most important tasks facing pharmacology is the creation of such systems that would minimize the harm caused by therapeutic drugs. One way to overcome these problems is to create drug delivery systems. Much attention is attracted the liposomes as delivery systems. They consist of natural components that can minimize toxicity in relation to the human body, so liposomes are interest to study. However, one of the limitations preventing the wide use of liposomes is their insufficient stability under physiological conditions. This property can lead to the fact that the drug will be released from the delivery system until the desired cells or tissues are reached, which means that it damages healthy cells. The problem of stability can be solved by systems called cerasomes. These are nanosized spherical particles consisting of the lipid bilayer as well as liposomes, but their surface is modified by a silicon polymer network. Liposomal nanohybrid cerasomes have been developed based on organoalkoxysilane through a sol-gel reaction in combination with self-assembly process. Among inorganic materials, silicon is an excellent choice to form hydrophilic surface shell due to its high chemical resistance, optical transparency and low physiological toxicity. In addition, cerasomes have better biocompatibility than silicon nanoparticles that have a similar size. They are inert and exhibit less cytotoxicity. Cerasomes are very convenient to store for a certain time due to their physical and chemical properties. Equally important is the fact that cerasomes are capable of encapsulate a wide range of drug molecules. Water-soluble drugs are built into the internal field of the vesicles, and hydrophobic drugs are built into the bilayer lipid membrane. So cerasomes can solve many problems associated with drug molecules like low drug solubility, fast clearance rates, non-specific toxicity, thereby enhancing therapeutic efficiency and reducing side effects. Also, various functional molecules can be included to cerasomes that show thermo-, light-, pH- or multi sensitive properties by chemical conjugation with different molecules in order to modulate the release behavior of the drug. Therefore, cerasomes, serving as delivery carriers, possess great potential for clinical applications due to their unique advantages. This review will summarize the progress of liposomal nanohybrid cerasomes and their applications as drug nanocarriers, transfection of gene materials, systems for visualization and diagnosis of diseases using MRI and PDT. It presents some methods of the synthesis of cerasome-forming lipids to create stable systems of cerasomes. Various approaches of the formation of a siloxane network on their surface are considered. Various variants of modifications of cerasome-forming lipids are presented.

Synthetic asymmetric lipid-like organosilanes for liposomal nanohybrid cerasomes toward potential medical applications

The design and synthesis of lipidic organoalkoxysilanes with different higher fatty acids as hydrophobic acyl chains for the construction of bilayer vesicles called ‘cerasomes’ were accomplished and their properties, including hydrodynamic diameter, zeta potential and encapsulation efficiency of water-soluble doxorubicin, were determined. Experiments have shown that an asymmetric hydrophobic block makes it possible to obtain cerasomes with acceptable size and stability. At the same time, the drug loading is quite high.

Freeze-drying of liposomal nanohybrid cerasomes with cryoprotectants: In vitro and in vivo evaluation

ABSTRACTLiposomal nanohybrid cerasomes as a new type of drug carrier has been widely applied in the controlled release of drugs. However, such vesicles containing polysiloxane networks on the surface were liable to aggregate during the process of freeze-drying for routine storage. To solve this problem, several previously reported cryoprotectants including sucrose, mannitol, sodium alginate, and glucose were chosen for protecting the 10-hydroxycamptothecin-loaded liposomal nanohybrid cerasomes (The drug encapsulation efficiency was of 67.31 ± 7.42% and the drug loading content was of 6.73 ± 0.74%.) in freeze-drying process. It was found that liposomal nanohybrid cerasomes treated with mannitol can be well dispersed, and the results of particle size and zeta potential showed that the drug-loaded vesicles were well protected with mannitol. In vitro drug release and in vivo pharmacokinetic study showed that the optimal addition amount of mannitol was twice the mass of the drug-loaded vesicles, whereby the cumulative release profile and the pharmacokinetic parameters were similar in the freeze-dried and fresh vesicles.

EGFR-targeted liposomal nanohybrid cerasomes: theranostic function and immune checkpoint inhibition in a mouse model of colorectal cancer.

Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancers (CRCs), and programmed death ligand-1 (PD-L1) is an attractive target for CRC immunotherapy. Herein, we report the synthesis of porphyrin-containing liposomal nanohybrid cerasomes decorated with cetuximab, an anti-EGFR antibody, and conjugated with IRDye800CW and MRI contrast DOTA-Gd, to enable in vivo tumor detection and photodynamic therapy (PDT). Moreover, PD-L1 was added for adjuvant therapy. The antitumor efficacy of PDT combined with PD-L1 immunotherapy was assessed. EGFR-targeted nanoparticles showed the targeted imaging of tumors. EGFR-targeted PDT combined with PD-L1 immunotherapy was more effective against tumor growth than simultaneous albeit nontargeted nanoparticle delivery with laser irradiation plus PD-L1 immunotherapy. Thus, EGFR-targeted nanoparticles exhibited significant potential toward dual-modality imaging-guided precise PDT, combined with immunotherapy.

Liposomal nanohybrid cerasomes targeted to PD-L1 enable dual-modality imaging and improve antitumor treatments

Programmed death ligand-1 (PD-L1) is a central element in cancer therapies targeting immune checkpoints, and its expression is an important predictor of the therapeutic response. With recent approvals of therapeutic antibodies against PD-L1 and PD-1, noninvasive detection methods are now urgently needed to quantify PD-L1 expression in tumors and to evaluate the response to immune therapies. However, only few such methods are available. Thus, we fabricated nanohybrid liposomal cerasome nanoparticles loaded with the chemotherapeutic drug paclitaxel, and evaluated their value as a theranostic agent. The particles are also decorated with PD-L1 antibody to enable specific targeting, and are dual-labeled to enable near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI) in vivo. Results showed that in vivo NIRF and MRI imaging following intravenous injection of cerasomes revealed a strong positive contrast for tumors, indicating long-lived enhancement of relevant signals. Moreover, the cerasomes were more effective against tumors and metastasis in comparison to simultaneous but nontargeted delivery of PD-L1 antibody and paclitaxel. Taken together, the data indicate that targeted, dual-labeled cerasomes are good theranostic agents for MRI/NIRF dual-mode detection and treatment of solid tumors in situ.

Liposomal nanohybrid cerasomes as an ideal drug/gene delivery system

Liposomal nanohybrid cerasomes as an ideal drug/gene delivery system

Safety evaluation of liposomal nanohybrid cerasomes and their application in the release of 10-hydroxycamptothecin

Cerasomes, a novel type of organic–inorganic liposomal nanohybrid with a silicate surface, has attracted a great deal of attention as a perfect substitute for liposomes due to its good morphological stability.

Design and Synthesis of Lipidic Organoalkoxysilanes for the Self‐Assembly of Liposomal Nanohybrid Cerasomes with Controlled Drug Release Properties

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.

Cerasomal doxorubicin with long-term storage stability and controllable sustained release

Liposomal nanohybrid cerasomes display a remarkable ability to maintain their size and retain encapsulated doxorubicin (DOX) over a period of 90days under storage conditions in solution compared with liposomes and liposils. Cerasomes retained 92.1±2.9% of the drug payload after 90days storage, much more than liposomes (35.2±2.5%) and liposils (53.2±5.5%). Under physiologically relevant conditions cerasomes exhibit a low initial burst in the first 5h and subsequent sustained release of DOX over the next 150h. Moreover, the magnitude of the initial burst and the rate of sustained release of DOX from cerasomes can be modulated by incorporating dipalmitoylphosphatidylglycerol (DPPG) in the cerasome structure and altering the ratios of the cerasome-forming lipid and phospholipids. Consequently, a wide range of release profiles can be achieved by altering the vesicle composition. Finally, human ovarian cancer cells are effectively killed by DOX released from cerasomes. Together these results suggest that cerasomes may be a promising drug delivery system for the long-term storage and controllable sustained release of the anticancer drug DOX.

Free-standing liposomal nanohybrid cerasomes as ideal materials for sensing of cupric ions

Super-stable and free-standing cerasomes with inorganic polyorganosiloxane surfaces were developed for the sensing of Cu(2+) by encapsulating Nile red (NR) dye as a fluorescence reporter. 1,2-Dimynistoyl-sn-glycero-3-phosphatidylethanolamine (DMPE) was incorporated into the cerasomes to serve as the chelating agent for cupric ions. The intraparticle energy transfer from NR to Cu(2+) caused the fluorescence quenching of NR, showing the prospect of these cerasomes as a fluorescence "turn-off" sensor for the detection of trace copper ions.

Stabilized liposomal nanohybrid cerasomes for drug delivery applications

Paclitaxel loaded cerasomes exhibited sophisticated controlled release behavior and remarkably high stability towards surfactant solubilization, long-term storage, acidic treatment, and all factors susceptible to destabilize conventional liposomes, demonstrating that liposomal nanohybrid cerasomes can be a new promising drug delivery system.