Liposomal Drug Research Articles

LXR inhibitor SR9243-loaded immunoliposomes modulate lipid metabolism and stemness in colorectal cancer cells

Reprogrammed metabolism and active stemness contribute to cancer stem cells' (CSCs) survival and tumorigenesis. LXR signaling regulates the metabolism of different cancers. A selective LXR inhibitor, SR9243 (SR), can target and eradicate non-CSC tumor cells. CD133 is a stem marker in solid tumors-associated CSCs within the active lipogenesis, and anti-CD133 mAb targeting liposomal drug delivery systems expected to increase drug internalization and improve the therapeutic efficacy of poor-in water solubility drugs, e, g., SR. In this study, anti-CD133 mAbs-targeted Immunoliposomes (ILipo) were developed for specific delivery of SR into MACS-enriched CD133 + CSCs and induce their functional effects. Results have shown that ILipo having an average size of 64.79nm can encapsulate SR in maximum proportion, and cell association studies have shown cationic ILipo and targeting CD133 provide the CSCs binding. Also, FCM analysis of RhoB has demonstrated that the ILipo uptake was higher in CD133 + CSCs than in the non-targeted liposomes. ILipo-SR was significantly more toxic in CD133 + CSCs compared to the free SR and non-targeted ones. More efficient than Lipo-SR, ILipo-SR improved the reduction of clonogenicity, stemness, and lipogenesis in CD133 + CSCs in vitro, boosted ROS generation, and induced apoptosis. Our study revealed the dual targeting of CD133 and LXR appears to be a promising strategy for targeting CD133 + CSCs-presenting dynamic metabolism and self-renewal potentials.

Anti-Porphyromonas gingivalis nanotherapy for maintaining bacterial homeostasis in periodontitis

Periodontitis is caused by oral flora imbalance, which leads to immune imbalance. Porphyromonas gingivalis is a keystone pathogen in periodontitis, causing the blooming of inflammophilic microbes, and becoming dormant to resist antibiotics. Targeted interventions are needed to destroy this pathogen and collapse its inflammophilic flora. Therefore, a targeting nanoagent antibody-conjugated liposomal drug carrier with ginsenoside Rh2 (A-L-R) was developed for pleiotropic benefits. A-L-R showed high quality in high-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR), and transmission electron microscope (TEM) detection. Only P. gingivalis was influenced by A-L-R, as shown by live/dead cell staining and a series of antimicrobial effects assays. With fluorescence in situ hybridization (FISH) staining and in propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR), the clearance of P. gingivalis by A-L-R was more than for other groups, and only the proportion of P. gingivalis was reduced by A-L-R in monospecies culture. Moreover, in a periodontitis model, A-L-R targeted P. gingivalis with high efficiency and low toxicity, maintaining homeostasis with a relatively stable oral microflora. This targeting nanomedicine offers new strategies for periodontitis therapy, providing a foundation for the prevention and treatment of periodontitis.

Using Liposomal and Intranasal Drugs and Pioglitazone for the Treatment and Prevention of Alzheimer’s Disease (Review)

Using Liposomal and Intranasal Drugs and Pioglitazone for the Treatment and Prevention of Alzheimer’s Disease (Review)

Interaction of neutral and protonated Tamoxifen with the DPPC lipid bilayer using molecular dynamics simulation

Tamoxifen as an antiestrogen is successfully applied for the clinical treatment of breast cancer in pre- and post-menopausal women. Due to the side effects related to the oral administration of Tamoxifen (such as deep vein thrombosis, pulmonary embolism, hot flushes, ocular disturbances and some types of cancer), liposomal drug delivery is recommended for taking this drug. Drug encapsulation in a liposomal or lipid drug delivery system improves the pharmacokinetic and pharmacodynamic properties. In this regard, we carried out 200-ns molecular dynamics (MD) simulations for three systems (pure DPPC and neutral and protonated Tamoxifen-loaded DPPC). Here, DPPC is a model lipid bilayer to provide us with conditions like liposomal drug delivery systems to investigate the interactions between Tamoxifen and DPPC lipid bilayers and to estimate the preferred location and orientation of the drug molecule inside the bilayer membrane.Properties such as area per lipid, membrane thickness, lateral diffusion coefficient, order parameters and mass density, were surveyed. With insertion of neutral and protonated Tamoxifen inside the DPPC lipid bilayers, area per lipid and membrane thickness increased slightly. Also, Tamoxifen induce ordering of the hydrocarbon chains in DPPC bilayer. Analysis of MD trajectories shows that neutral Tamoxifen is predominantly found in the hydrophobic tail region, whereas protonated Tamoxifen is located at the lipid–water interface (polar region of DPPC lipid bilayers).

Optimization of dihydrosphingomyelin/cholesterol mol ratio in topotecan-loaded liposomes to enhance drug retention and plasma half-life by understanding physicochemical and thermodynamic properties of the lipid membrane

Robust retention of drugs in liposomes is one of the most critical factors for liposomal drug formulation. It improves loading efficiency of the active pharmaceutical ingredient (API), stability during long-term storage, and half-life of the drug in the body. This study deductively optimized the lipid composition of topotecan-loaded liposome using dihydrosphingomyelin (DHSM), cholesterol (Chol), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE PEG) for intravenous injection by thermodynamic and fluidity analyses of the liposome membrane. High efficiency in topotecan loading was achieved in the range of the liquid-ordered phase (egg-derived DHSM/Chol molar ratio 70/25% or a higher Chol ratio with PEG constant at 5 mol%) as predicted by thermodynamic analysis. The egg-derived DHSM/Chol/PEG mol ratio that minimizes topotecan leakage was estimated to be 57/38/5 via electron spin resonance (ESR) for fluidity analysis. The optimized liposome significantly prolonged the half-life of topotecan in blood compared to non-liposomal topotecan. To minimize the risk of virus contamination and ensure easier quality control for clinical application, synthetic DHSM was used in the optimized formulation of topotecan encapsulated liposome instead of egg-derived DHSM (named FF-10850). The physicochemical and pharmacokinetic profiles of FF-10850 were equivalent to those of the liposome prepared using egg-derived DHSM and >99% drug retention was maintained for over 24 months under refrigeration, indicating stable encapsulation and prolonged blood circulation.

Development of a Liposomal Gel for Prolonged Ophthalmic Soluble Drug Delivery

AbstractLiposome, as a drug delivery vehicle, entraps drugs, releases them sustainably, and modifies release patterns. This entrapment has diminished exposure of the drug to the eye medium, which could minimize adverse effects. In this investigation, 18 formulations in 3 key categories (liposome, gel and lipogel) of cromolyn sodium (CS) were prepared and evaluated as a water‐soluble drug. Then, liposome formulations (L1‐L6) were developed using the thin‐film hydration method. The macroscopic and microscopic assessments comprised drug entrapment efficiency, release rate, release mechanism, liposome stability, and vesicle size were evaluated to evaluate liposomes and lipogel. The results revealed that applying cholesterol in formulations ranging from 33 % to 44 % w/w increased the liposome drug entrapment efficiency, stability, and release time. The optimum phosphatidylcholine (PC) ratio to cholesterol in the L4 formulation was 2 : 1, which prolonged drug release time by up to 5 hours. The carbomer® 934 containing lipogel (0.5 % w/v) showed the longest release time (9 hours) with a zero‐order release. CS release from HPMC (2 % w/v) lipogel was assumed to follow first‐order release kinetics. The prolongation of drug release time in a carboxymethylcellulose lipogels was shorter than carbomer® 934 (5 hours). Finally, a sustained release formulation of CS liposome was produced; it was developed as lipogels to enhance its release duration; finally, release kinetic were modified.

A Novel Strategy for Liposomal Drug Separation in Plasma by TiO2 Microspheres and Application in Pharmacokinetics.

Liposomes are nano-scale materials with a biofilm-like structure. They have excellent biocompatibility and are increasingly useful in drug delivery systems. However, the in vivo fate of liposomal drugs is still unclear because existing bioanalytical methods for quantitation of total and liposomal-encapsulated drugs have limits. A novel strategy for liposomal-encapsulated drug separation from plasma was developed via the specific coordinate binding interaction of TiO2 microspheres with the phosphate groups of liposomes. Liposomal-encapsulated docetaxel was separated from plasma by TiO2 microspheres and analyzed by the UPLC-MS/MS method. The amount of TiO2, pH of the dilutions, plasma dilution factors and incubation time were optimized to improve extraction recovery. The characterization of the adsorption of liposome-encapsulated drugs by TiO2 microspheres was observed by electron microscopy. For understanding the mechanism, pseudo-first and the pseudo-second order equations were proposed for the adsorption process. The study fully validated the method for quantitation of liposomal-encapsulated in plasma and the method was applied to the pharmacokinetic study of docetaxel liposomes. The encapsulated docetaxel had a concentration range of 15-4000 ng/mL from the plasma sample using a TiO2 extraction method. Successful method validation proved the method was sensitive, selective and stable, and was suitable for quantitation of docetaxel liposomes in plasma samples. Extraction recovery of this method was higher than that of SPE method. As shown in electron microscopy, the liposomes adsorbed on TiO2 microspheres were intact and there was no drug leakage. The study proposed pseudo-first and the pseudo-second order equations to facilitate the adsorption of liposomal drugs with TiO2 microspheres. The proposed strategy supports the pharmacokinetic study of docetaxel liposomes in rats. TiO2 extraction method was stable, reproducible, and reliable for quantitation of encapsulated docetaxel. Because of versatility of lipids, it is expected to a universal bioanalysis method for the pharmacokinetic study of liposomes.

Liposomal Drug Delivery System as an Emerging Technique for Treatment of “Neurodegenerative Diseases”

Abstract:: In the last decade, the onset of neurodegenerative diseases (ND) has been strongly wide-spread due to the rapid increase in the world population. There are many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, spinal muscular atrophy, Levy body disease, etc. Alzheimer’s disease and Parkinson’s disease are most commonly found. Neurodegenerative diseas-es occur due to the degradation of neurons in the brain and the spinal cord. The diagnosis of both diseases has increased, however, the successful treatment is still very limited because of the lower ability of the drug to cross the blood-brain barrier (BBB). It is a big challenge to deliver the drug to the brain, because only small and lipid-soluble agents cross the BBB, by considering this assump-tion, the liposomal drug delivery system is considered one of the effective treatments in neuro-degenerative diseases. Liposomes are considered to be an ideal carrier as they are flexible, biocom-patible, and can carry different types of therapeutic molecules across the BBB. This review focus on the potential use of lipid delivery system in the treatment of neurodegenerative diseases and the ap-plication of liposomes in Alzheimer's disease and Parkinson’s disease.

Palladium responsive liposomes for triggered release of aqueous contents

Palladium (Pd) is a promising metal catalyst for novel bioorthogonal chemistry and prodrug activation. This report describes the first example of palladium responsive liposomes. The key molecule is a new caged phospholipid called Alloc-PE that forms stable liposomes (large unilamellar vesicles, ∼220 nm diameter). Liposome treatment with PdCl2 removes the chemical cage, liberates membrane destabilizing dioleoylphosphoethanolamine (DOPE), and triggers liposome leakage of encapsulated aqueous contents. The results indicate a path towards liposomal drug delivery technologies that exploit transition metal triggered leakage.

Enhancing electroporation-induced liposomal drug release in suspension and solid phases

When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.

Liposomal form of erlotinib for local inhalation administration and efficiency of its transport to the lungs

This contribution is focused on the preparation of a liposomal drug delivery system of erlotinib resisting the nebulization process that could be used for local treatment of non-small-cell lung cancer. Liposomes with different compositions were formulated to reveal their influence on the encapsulation efficiency of erlotinib. An encapsulation efficiency higher than 98 % was achieved for all vesicles containing phosphatidic acid (d ≈ 100 nm, ζ = – 43 mV) even in the presence of polyethylene glycol (d ≈ 150 nm, ζ = – 17 mV) which decreased this value in all other formulas. The three most promising formulations were nebulized by two air-jet and two vibrating mesh nebulizers, and the aerosol deposition in lungs was calculated by tools of computational fluid and particle mechanics. According to the numerical simulations and measurements of liposomal stability, air-jet nebulizers generated larger portion of the aerosol able to penetrate deeper into the lungs, but the delivery is likely to be more efficient when the formulation is administered by Aerogen Solo vibrating mesh nebulizer because of a higher portion of intact vesicles after the nebulization. The leakage of encapsulated drug from liposomes nebulized by this nebulizer was lower than 2 % for all chosen vesicles.

Clot-Targeted Antithrombotic Liposomal Nanomedicine Containing High Content of H2O2-Activatable Hybrid Prodrugs.

Liposomes have been extensively explored as drug carriers, but their clinical translation has been hampered by their low drug-loading content and premature leakage of drug payloads. It was reasoned that vesicle-forming prodrugs could be incorporated into the lipid bilayer at a high molar fraction and therefore serve as a therapeutic agent as well as a structural component in liposomal nanomedicine. Boronated retinoic acid (BORA) was developed as a prodrug, which can self-assemble with common lipids to form liposomes at a high molar fraction (40%) and release all-trans retinoic acid (atRA) and hydroxybenzyl alcohol (HBA) simultaneously, in response to hydrogen peroxide (H2O2). Here, we report fucoidan-coated BORA-incorporated liposomes (f-BORALP) as clot-targeted antithrombotic liposomal nanomedicine with H2O2-triggered multiple therapeutic actions. In the mouse model of carotid arterial thrombosis, f-BORALP preferentially accumulated in the injured blood vessel and significantly suppressed thrombus formation, demonstrating their potential as targeted antithrombotic nanomedicine. This study also provides valuable insight into the development of vesicle-forming and self-immolative prodrugs to exploit the benefits of liposomal drug delivery.

Effect of Cellular and Microenvironmental Multidrug Resistance on Tumor-Targeted Drug Delivery in Triple-Negative Breast cancer.

Multidrug resistance (MDR) reduces the efficacy of chemotherapy. Besides inducing the expression of drug efflux pumps, chemotherapy treatment alters the composition of the tumor microenvironment (TME), thereby potentially limiting tumor-directed drug delivery. To study the impact of MDR signaling in cancer cells on TME remodeling and nanomedicine delivery, we generated multidrug-resistant 4T1 triple-negative breast cancer (TNBC) cells by exposing sensitive 4T1 cells to gradually increasing doxorubicin concentrations. In 2D and 3D cell cultures, resistant 4T1 cells are presented with a more mesenchymal phenotype and produced increased amounts of collagen. While sensitive and resistant 4T1 cells showed similar tumor growth kinetics in vivo, the TME of resistant tumors was enriched in collagen and fibronectin. Vascular perfusion was also significantly increased. Fluorophore-labeled polymeric (∼10nm) and liposomal (∼100nm) drug carriers were administered to mice with resistant and sensitive tumors. Their tumor accumulation and penetration were studied using multimodal and multiscale optical imaging. At the whole tumor level, polymers accumulate more efficiently in resistant than in sensitive tumors. For liposomes, the trend was similar, but the differences in tumor accumulation were insignificant. At the individual blood vessel level, both polymers and liposomes were less able to extravasate out of the vasculature and penetrate the interstitium in resistant tumors. In a final in vivo efficacy study, we observed a stronger inhibitory effect of cellular and microenvironmental MDR on liposomal doxorubicin performance than free doxorubicin. These results exemplify that besides classical cellular MDR, microenvironmental drug resistance features should be considered when aiming to target and treat multidrug-resistant tumors more efficiently.

Cholesterol concentration effect on bilayer membranes and its role in designing efficient liposomal drug delivery systems.

Liposomal drug delivery systems provide a versatile therapeutic platform for treating numerous diseases. Cholesterol, as a common component of many liposomal drug delivery systems, plays a crucial role in enhancing mechanical strength and decreasing the permeability of biomembranes. However, the ratio required for a proper formulation is poorly recognized. In this study, all-atom molecular dynamics simulations are performed to characterize the effect of cholesterol concentration in bilayers. To prepare liposomes, we simulate DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) phospholipid combined with different molar ratios of cholesterol (100, 80-20, 70-30, and 60-40%) in both planar and spherical bilayers. Furthermore, it has been quantified how a range of bilayer properties, including area per lipid, leaflet interdigitation, membrane thickness, and lipid Scd order parameters, are altered by variation in concentrations of lipid and cholesterol. Therefore, the most suitable amount of cholesterol and lipid to prepare stable and controlled drug release vehicles is obtained by screening the lipid and cholesterol ratio arrangement. Compared to membranes without cholesterol, the influence of cholesterol on lipid bilayers is revealed. These results provide a better understanding of the fundamental characteristics of the structure and dynamics of cholesterol-containing membranes. By revealing molecular details of interactions between cholesterol and phospholipids, these simulations accurately represent atomic-level characteristics of the planar and spherical bilayers. The simulations presented here shed light on the workings and limitations of liposomal drug delivery technology and establish a computational framework for the rational design of liposomes in drug delivery systems.

ENCAPSULATION OF EUCALYPTUS LEAVES PHYTOPRODUCTS INTO LIPOSOMAL NANOPARTICLES AND STUDY OF THEIR ANTIBACTERIAL ACTIVITY AGAINST STAPHYLOCOCCUS AUREUS IN VIVO

Plant oils are high effective active pharmaceutical ingredients, but the extremely low bioavailability of lipophilic compounds limits their use in drugs. The encapsulation of essential oils into nanoparticles are actively studied. The aim of the research was to prepare liposomal forms of eucalyptus leaves extract and Chlorophyllipt and to study their antibacterial activity. Liposomal forms of Chlorophyllipt and eucalyptus oil extract was prepared using egg phosphatidylcholine and cholesterol by high pressure homogenization and sonication method. The average particle sizes of liposomal Chlorophyllipt and liposomal eucalyptus extract were 156.5 and 210.4 nm, respectively. Active pharmaceutical ingredient encapsulation in liposomal Chlorophyllipt and liposomal eucalyptus extract were at least 85% and at least 90%, respectively. Antibacterial activity of liposomal drugs was studied in white mice with model of staphylococcal infection, initiated by Staphylococcus aureus ATTC 209. The use of liposomal eucalyptus oil and liposomal Chlorophyllipt demonstrates no toxicity in mice. Both investigated drugs demonstrated antibacterial activity against Staphylococcus aureus in mice. A single administration of the liposomal drugs increased the survival rate up to 30-40% compared with model animals. Double administration of liposomal drugs both in liquid form and in lyophilized form increased the survival rate by at least 70 %. Moreover, in the group of animals treated liposomal eucalyptus oil, the number of surviving animals was 100%, while in a group of liposomal Chlorophyllipt it was 80%.

Screening of Zwitterionic Liposomes with Red Blood Cell‐Hitchhiking and Tumor Cell‐Active Transporting Capability for Efficient Tumor Entrance

AbstractThe active transport of nanoparticles into the solid tumor through cell transcytosis has shown great promise in cancer nanomedicine, but it is challenging to develop efficient active transporting nanomedicines with the potential for clinical translation. Here, a type of tertiary amine oxide (TAO)‐containing zwitterionic liposomal nanocarriers is developed that can hitchhike red blood cells (RBCs) to tumor blood vessels and enter solid tumors through transcytosis. To boost the active‐transporting capability, a library of the TAO liposomes (TAOLs) with different chemical structures and particle sizes is constructed and screened by their stability and active transporting capability. Two types of TAOLs are identified that can induce efficient tumor cell transcytosis through rapid macropinocytosis and endoplasmic reticulum/Golgi‐involved exocytosis. It is found that these zwitterionic TAOLs can hitchhike RBCs to gain long blood circulation, get off the cell at the tumor site, effectively enter the tumor through transcytosis, and infiltrate the whole tumor. The chemotherapeutic drug‐loaded liposomes can stop the tumor progression of mice bearing human hepatocellular carcinoma HepG2 cells, exhibiting superior antitumor activity compared to the traditional liposomal drug. This study demonstrates a strategy to construct effective active transporting liposomal nanomedicines for efficient tumor entrance.

Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. Data availabilityData will be made available on request.

How wound environments trigger the release from Rifampicin-loaded liposomes

BackgroundChronic wounds often contain high levels of proinflammatory cytokines that prolong the wound-healing process. Patients suffering from these conditions are likely to benefit from topical rifampicin therapy. Although recent research indicates considerable anti-inflammatory properties of the antibiotic, currently, there are no commercial topical wound healing products available. To address this medical need, a liposomal drug delivery system was developed. A mechanistic investigation outlined major influences of wound environments that affect the release kinetics and, as a consequence, local bioavailability. MethodsLiposomes were prepared using the thin-film hydration method and subsequently freeze-dried at the pilot scale to improve their stability. We investigated the influence of oxidation, plasma proteins, and lipolysis on the in vitro release of rifampicin and its two main degradation products using the Dispersion Releaser technology. A novel simulated wound fluid provided a standardized environment to study critical influences on the release. It reflects the pathophysiological environment regarding pH, buffer capacity, and protein content. ResultsDuring storage, the liposomes efficiently protect rifampicin from degradation. After the dispersion of the vesicles in simulated wound fluid, despite the significant albumin binding (>70%), proteins have no considerable effect on the release. Also, the presence of lipase at pathophysiologically elevated concentrations did not trigger the liberation of rifampicin. Surprisingly, the oxidative environment of the wound bed represents the strongest accelerating influence and triggers the release. ConclusionA stable topical delivery system of rifampicin has been developed. Once the formulation comes in contact with simulated wound fluid, drug oxidation accelerates the release. The influence of lipases that are assumed to trigger the liberation from liposomes depends on the drug-to-lipid ratio. Considering that inflamed tissues exhibit elevated levels of oxidative stress, the trigger mechanism identified for rifampicin contributes to targeted drug delivery.

Polysaccharide-modified liposomes and their application in cancer research.

Nanodrug delivery systems have been widely used in cancer treatment. Among these, liposomal drug carriers have gained considerable attention due to their biocompatibility, biodegradability, and low toxicity. However, conventional liposomes have several shortcomings, such as poor stability, rapid clearance, aggregation, fusion, degradation, hydrolysis, and oxidation of phospholipids. Polysaccharides are natural polymers of biological origin that exhibit structural stability, excellent biocompatibility and biodegradability, flexibility, non-immunogenicity, low toxicity, and targetability. Therefore, they represent a promising class of polymers for the modification of the surface properties of liposomes to overcome their shortcomings. In addition, polysaccharides can be readily combined with other materials to develop new composite materials. Hence, they represent the optimal choice for liposomal modification to improve pharmacokinetics and clinical utility. Polysaccharide-coated liposomes exhibit better stability, drug release kinetics, and cellular uptake than conventional liposomes. The oncologic application of polysaccharide-coated liposomes has become a research hotspot. We summarize the preparation, physicochemical properties, and antineoplastic effects of polysaccharide-coated liposomes to facilitate antitumor drug development.

Nanoparticles in Clinical Trials: Analysis of Clinical Trials, FDA Approvals and Use for COVID-19 Vaccines.

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines-Pfizer and Moderna-that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.