Pharmaceutical Nanocarriers Research Articles

Ambient pressure dried graphene oxide-silica composite aerogels as pharmaceutical nanocarriers

Ambient pressure dried graphene oxide-silica composite aerogels as pharmaceutical nanocarriers

Pair Potential between Poloxamer 407 Micelles in 14 wt % Aqueous Solution Clarifying the Sol-Gel-Sol Transition by Temperature Rise.

Poloxamer 407 (P407) is used as a safety-guaranteed, invaluable pharmaceutical nanocarrier. The aqueous solution of P407 exhibits sol-to-gel and gel-to-sol transitions, specifically during a temperature rise. Here, we develop a method to determine the pair potential between colloidal particles based primarily on experimental small-angle scattering data. Using this approach, the pair potential between the P407 micelles in the sol-gel-sol transition state is revealed without prelimiting any type of interaction forces. The results indicate that the increase in the attractive interaction contributes to enhancing the volume fraction, which is the decisive parameter for the gelation in terms of the Alder transition theory, i.e., the fluid-to-crystal phase transition of the hard-sphere model in the micelle system. This study demonstrates that one of the key mechanisms of the gel-to-sol transition upon heating is the enhancement of the structural fluctuation due to widening of the potential well in the intermicellar pair potential.

Multivariate Analysis of Cellular Uptake Characteristics for a (Co)polymer Particle Library.

Controlling cellular responses to nanoparticles so far is predominantly empirical, typically requiring multiple rounds of optimization of particulate carriers. In this study, a systematic model-assisted approach should lead to the identification of key parameters that account for particle properties and their cellular recognition. A copolymer particle library was synthesized by a combinatorial approach in soap free emulsion copolymerization of styrene and methyl methacrylate, leading to a broad compositional as well as constitutional spectrum. The proposed structure-property relationships could be elucidated by multivariate analysis of the obtained experimental data, including physicochemical characteristics such as molar composition, molecular weight, particle diameter, and particle charge as well as the cellular uptake pattern of nanoparticles. It was found that the main contributors for particle size were the polymers' molecular weight and the zeta potential, while particle uptake is mainly directed by the particles' composition. This knowledge and the reported model-assisted procedure to identify relevant parameters affecting particle engulfment of particulate carriers by nonphagocytic and phagocytic cells can be of high relevance for the rational design of pharmaceutical nanocarriers and assessment of biodistribution and nanotoxicity, respectively.

Abstract 1995: 2C5-surface modified nanocarriers targeting neutrophil extracellular traps

Abstract Background: Neutrophil extracellular traps (NETs) are composed of processed chromatin bound to granular and selected cytoplasmic proteins and released by neutrophils. NETs consist of smooth filaments composed of stacked nucleosomes. Fully hydrated NETs have a cloud-like appearance and occupy a space 10-15-fold larger than the volume of the cells they originate from. DNases are the enzymes that cleave extracellular DNA including NETs. Together with their protective role in microbial infections, NETs are involved in multiple pathological processes and represent key events in a variety of pathologies including cancer, autoimmunity, and cardiovascular disease. Sites of NETs concentration are dangerous for the host if the process of NETs formation becomes chronic or the mechanism of NETs removal does not work. NETosis has been linked to the development of periodontitis, cystic fibrosis, type 2 diabetes, COVID-19 or rheumatoid arthritis as well as cancer progression. Purpose: Thus, the destruction of NETs is of primary significance in many pathologies. In our approach, we are focusing on mimicking one of the natural mechanisms of destroying excessive NETs by delivering deoxyribonuclease I to the specific site of pathological NETs accumulation by modifying the nanoparticles using an anti-nucleosome monoclonal antibody (2C5). The antibody is specific to nucleosomes and can recognize histones in NETs. DNase I is U.S. Food and Drug Administration (FDA)-approved active component and is commonly used in therapeutic methods of modern medicine for cystic fibrosis to clear extracellular DNA fibers in the lungs and systemic lupus erythematosus. Recent findings have also shown the effectiveness of DNase I in the digestion of NETs. However, the low serum stability and fast deactivation by environmental stimuli have been considered as the limiting factors for clinical applications of DNase I, which can be overcome by its targeted specific delivery in pharmaceutical nanocarriers. Methods: In this study, we generate NETs in vitro using human neutrophils and HL-60 cells differentiated into granulocyte-like cells. We used interleukin-8, lipopolysaccharide from E.Coli (LPS), phorbol myristate acetate (PMA), and calcium ionophore A23187 (CI) to generate the NETs. We confirmed the specificity of 2C5 toward NETs by ELISA, which showed that it binds to NETs with the specificity like that for purified nucleohistone substrate. We further utilized that feature to create two delivery systems (liposomes and micelles) for DNAse I enzyme to destroy NETs, which was confirmed by staining NETs with SYTOX Green dye and followed by flow cytometric measurements and microscopic images. Conclusions: Our results suggest that 2C5 could be used to identify and visualize NETs and serve as a ligand for NET-targeted diagnostics and therapies. Also, we proved that our carrier can successfully deliver DNase to NETs to provide their degradation. Citation Format: Nina Filipczak, Xiang Li, Gaurav Rajan Saawant, Diptanshu Pardeshi, Bharat Ashok Rajmalani, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin. 2C5-surface modified nanocarriers targeting neutrophil extracellular traps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1995.

Reduction-sensitive flower-like magnetomicelles based on PCL-ss-PEG-ss-PCL triblock copolymer as anti-cancer drug delivery system

Introducing an intelligent pharmaceutical nanocarrier for targeted drug release and reducing the side effects of chemotherapy is the main goal of many researchers. In this area, we synthesized amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL consisting of cystamine as a reduction sensitive linkage. The aqueous self-assembly of triblock copolymer in the presence of magnetic iron oxide nanoparticles (Fe3O4) and doxorubicin (DOX) led to the formation of reduction-sensitive flower like magnetomicelle containing DOX and Fe3O4. The innovative design based on intelligent flower like structure led to high drug loading content, reduce drug release in physiologic condition, fast degradation at targeted site and burst release of more content of drug at earlier time. The DOX loading content was about 19% and DOX- loaded magnetomicelles (D-LMM) showed more triggered release under redox conditions at pH = 5. The efficiency of D-LMM was compared with non-reduction sensitive control group (CD-LMM), free DOX and commercial product of liposomal DOX (LD) in vitro. The D-LMM showed significant improvement in cellular uptake and toxicity behavior on human breast adenocarcinoma MCF-7 cells in comparison to commercial LD and also displayed better results in the cytotoxicity and apoptosis/necrosis assays in comparison to CD-LMM.

Decoupling of dust cloud and embedding plasma for high electron depletion in nanodusty plasmas

In recent years nanoparticles have become key technological products, e.g., as coatings with tunable optical gap in third generation solar cells, as nanocrystals for photonic applications, and as pharmaceutical nanocarriers. In particle sources, that use reactive, nanodusty plasmas, a high dust density changes the properties of the dusty plasma compared to a dust free plasma considerably, as electron depletion leads to a reduced number of free electrons. This is called the Havnes effect and was central for the understanding of the famous spokes in Saturns rings. We see here, that it is also important for technological applications. Using self excited dust density waves (DDW) as a diagnostic tool, we completely characterize an argon discharge with embedded amorphous hydrocarbon nanoparticles of different size and density. The results show, that electron depletion governs the charge of dust grains, while the size of the particles has only a weak influence. The ion density and electric potential profile are almost independent of both, dust size as well as dust density. This suggests, that the rf generated plasma and the dust cloud seem to coexist and coupling of both is weak.

Biomimetic synthesis of iron oxide nanoparticles from Bacillus megaterium to be used in hyperthermia therapy

The suitable structural characteristics of magnetic nanoparticles have resulted in their widespread use in magnetic hyperthermia therapy. Moreover, they are considered a proper and operational choice for pharmaceutical nanocarriers. Using the biomimetic method, we were able to produce iron oxide magnetic nanoparticles from the bacterial source of PTCC1250, Bacillus megaterium, for therangostic diagnosis systems and targeted drug delivery. Some of the benefits of this method include mitigated environmental and biological dangers, low toxicity, high biocompatibility, cheap and short-term mass production possibilities in each synthesis round compared to other biological sources, simple equipment required for the synthesis; and the possibility of industrial-scale production. Bacillus megaterium is a magnetotactic bacteria (MTB) that has a magnetosome organelle capable of orienting based on external magnetic fields, caused by the mineralization of magnetic nanocrystals. Utilizing this capability and adding an iron nitrate solution to the bacterial suspension, we synthesized iron oxide nanoparticles. The extent of synthesis was measured using UV–visible spectrophotometry. The morphology was evaluated using FESEM. The crystallized structure was characterized using RAMAN and XRD. The size and distribution of the nanoparticles were assessed using DLS. The surface charge of the nanoparticles was measured using zeta potential. The synthesis of iron oxide nanoparticles was confirmed using FT-IR, and the magnetic property was measured using VSM. This study is continued to identify industrial and clinical applications.

A Comparative Study of Quercetin-Loaded Nanocochleates and Liposomes: Formulation, Characterization, Assessment of Degradation and In Vitro Anticancer Potential.

Quercetin, a flavonoid, has antioxidant and anti-inflammatory properties and the potential to inhibit the proliferation of cancer, but its therapeutic efficacy is lowered due to poor solubility and bioavailability. Quercetin-loaded nanocochleates (QN) were developed using a trapping method by the addition of calcium ions into preformed negatively charged liposomes (QL) prepared by a thin-film hydration method. Liposomes were optimized by varying the concentration of Dimyristoyl phosphatidyl glycerol and quercetin by applying D-optimal factorial design using Design-Expert® software. Stable rods were observed using TEM with an average particle size, zeta potential and encapsulation efficiency of 502 nm, −18.52 mV and 88.62%, respectively, for QN which were developed from spherical QL showing 111.06 nm, −40.33 mV and 74.2%, respectively. In vitro release of quercetin from QN and QL was extended to 24 h. Poor bioavailability of quercetin is due to its degradation in the liver, so to mimic in vivo conditions, the degradation of quercetin released from QL and QN was studied in the presence of rat liver homogenate (S9G) and results revealed that QN, due to its unique structure, i.e., series of rolled up solid layers, shielded quercetin from the external environment and protected it. The safety and biocompatibility of QL and QN were provenby performing cytotoxicity studies on fibroblast L929 cell lines. QN showed superior anticancer activity compared to QL, as seen for human mouth cancerKB cell lines. Stability studies proved that nanocochleates were more stable than liposomal formulations. Thus, nanocochleates might serve as pharmaceutical nanocarriers for the improved efficacy of drugs with low aqueous solubility, poor bioavailability, poor targeting ability and stability.

Development, Characterization and Short-Term Stability Studies of Chitosan-Lipid Hybrid Nanocarrier System

Pharmaceutical nanocarriers have recently been widely used to improve drug performance and reduce side effects. They have been shown to be effective for controlled release, sustained release, and targeted delivery. It is also possible to accomplish effective drug utilization, improve permeability, and attain selectivity of drugs. Chitosan polymer attracted the attention of formulation scientists due to its biocompatible, biodegradable nature and utility in drug delivery as a permeation enhancer, as well as its ability to achieve sustained, controlled, site-specific release. Furthermore, it has been shown to be an efficacious counter to both gram -ve and +ve bacteria. Chitosan is a useful carrier for a variety of nanosystems. Targeting the intestinal region of the gastrointestinal track the lymphatic system and other novel approaches will be possible if combined with long-chain fatty lipids. The present work developed a chitosan-lipid nanocarrier system (CLNS) by melt emulsification with sonication. The prepared system was assessed for size analysis, and determination of PDI, zeta potential and the findings were 221.3 ± 3.2 nm, 0.251 ± 0.01, 26.9 ± 2.2 mV, respectively. FTIR analysis reveals the polymer’s compatibility with lipid. DSC and XRD analysis confirmed the presence of amorphous CLNS. The TEM findings suggest that CLNS have a nearly spherical shape with a smooth surface morphology. Furthermore, the carrier system was tested for short-term stability studies, and it was observed that the system is more stable at refrigerated (4℃) and normal environmental conditions (25 ± 2℃ / 60 ± 5% RH) than that of the accelerated conditions (40 ± 2℃/75 ± 5% RH).

Application of Non-Destructive Testing Techniques (NDTT) to Characterize Nanocarriers Used for Drug Delivery: A Mini Review

The synthesis of tailored and highly engineered multifunctional pharmaceutical nanocarriers is an emerging field of study in drug delivery applications. They have a high surface-area-to-volume ratio, aiding the targeted drug’s biodistribution and pharmacokinetic properties. Therefore, the characterization of nanocarriers is critical for understanding their physicochemical properties, which significantly impact their molecular and systemic functioning. To achieve specific goals, particle size, surface characteristics, and drug release properties of nanocarriers must be managed. This mini review provides an overview of the applications of non-destructive testing techniques (NDTT) to reveal the characteristics of nanocarriers, considering their surface charge, porosity, size, morphology, and crystalline organization. The compositional and microstructural characterization of nanocarriers through NDTT, such as dynamic light scattering, X-ray diffraction, confocal laser scanning microscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance spectroscopy, have been comprehensively reviewed. Furthermore, NDTT is only used to characterize physicochemical parameters related to the physiological performance of nanocarriers but does not account for nanocarrier toxicity. Hence, it is highly recommended that in the future, NDTT be developed to assess the toxicity of nanocarriers. In addition, by developing more advanced, effective, and precise techniques, such as machine vision techniques using artificial intelligence, the future of using NDTT for nanocarrier characterization will improve the evaluation of internal quality parameters.

Improving the Therapeutic Performance of Glycyrrhiza Glabra Hydroalcoholic Extract Using Liposomal Nano-carriers and Their Characterization

Background: The use of plants as therapeutic drugs has long been common among human beings. The Glycyrrhiza glabra is one of the medicinal plants with many therapeutic properties. However, using this herb in traditional methods faces some challenges. The use of pharmaceutical nano-carriers such as liposomes is one of the new strategies to overcome these challenges. In this regard, the current study aimed to synthesize and characterize liposomal nano-carriers containing the G. glabra hydroalcoholic extract to improve its therapeutic effects. Materials and Methods: After the extraction of the G. glabra root by the Soxhlet method, nano-liposomes containing G. glabra extracts were synthesized by the thin-film preparation method. Then, the encapsulation efficiency (EE) rate and drug release pattern of nanoliposome were examined using the spectrophotometry method. Next, physicochemical properties such as size, zeta potential, morphology, and non-interaction of the nano-system with the extract were investigated by dynamic-light-scattering (DLS), atomic force microscope (AFM), and Fourier transform infrared spectroscopy (FTIR) methods, and finally, the toxicity of the nano-system on human foreskin fibroblast cells was assessed using the MTT method. Results: Nano-liposomes containing licorice extracts with the EE of 2.3±75.32% were from the type of slow release and controlled release, having a size of 111.4±1.2 nm, a surface charge of -53.6±6.3, and a dispersion index of 0.210±0.13, and they had no interaction with the loaded extract. The results of the MTT test also demonstrated that the synthesized nano-liposomes were non-toxic on normal cells. Conclusion: Overall, the findings proved that synthesized nano-liposomes with proper physicochemical properties can be a suitable carrier for the G. glabra extract and thus cause stability and improve the therapeutic effects of this herbal extract as a medicinal plant.

COOH-Terminated Silicon Quantum Dots as a Highly Efficient Drug Nanocarrier for Targeted Tumor Cell Imaging.

Fluorescent silicon quantum dots (SiQDs) characterized by exceptional photostability and colloidal robustness as well as beneficial biocompatibility are fast becoming new pharmaceutical nanocarriers. With a view to efficiently loading cisplatin (CDDP) onto SiQDs, carboxylate group (COOH) terminated SiQDs were imperative because of chelate formation with CDDP. In this work, we employed a facial microwave irradiation route for rapidly synthesizing high-quality COOH-SiQDs through the use of 3-aminopropyl trimethoxy silane (APTMS) molecules to fulfil the role of silicon precursor and maleic acid (MA) as the agent for facilitating reduction. The SiQDs showed blue fluorescence with an associated photoluminescence quantum yield (PLQY) of 40.2%, the size of which was small at 3.2 ±0.6 nm, and long-lasting stability (an extensive range in pH (4-12) and concentrations of electrolytes reaching 3 Molarity of a solution of sodium chloride). As nanocarriers, carboxylic acids chelation generated a high loading of CDDP onto SiQDs (drug loading capacity, DLC up to 32.2% at pH = 9) and a drug release of CDDP up to 57.6% at pH = 5. Furthermore, the MTT assays demonstrated the non or low cytotoxicity of SiQDs and the role of the controlled release of SiQD-CDDP Finally, the prepared SiQD-CDDP were used for cell imaging, and further targeted labeling of some tumors after folic acid (FA) conjugation. These characteristics allow for the deployment of SiQDs as a highly efficient nanocarrier that facilitate the delivery of clinical drugs for the future.

Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect.

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

Polymer-Lipid Pharmaceutical Nanocarriers: Innovations by New Formulations and Production Technologies.

Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation.

Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers.

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy–safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy–safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.

Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects.

In the golden age of pharmaceutical nanocarriers, we are witnessing a maturation stage of the original concepts and ideas. There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. In this context, lipid nanoparticles have gained ground, since they are generally regarded as non-toxic, biocompatible and easy-to-produce formulations. Pharmaceutical applications of lipid nanocarriers are a burgeoning field for the transport and delivery of a diversity of therapeutic agents, from biotechnological products to small drug molecules. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic preformulation studies. The main applications, as well as the advantages that this type of nanovehicles offers in certain therapeutic scenarios are discussed. Next, pharmacokinetic aspects are described, such as routes of administration, absorption after oral administration, distribution in the organism (including brain penetration) and elimination processes. Safety and toxicity issues are also addressed. Our work presents an original point of view, addressing the biopharmaceutical aspects of these nanovehicles by means of descriptive statistics of the state-of-the-art of solid lipid nanoparticles research. All the presented results, trends, graphs and discussions are based in a systematic (and reproducible) bibliographic search that considered only original papers in the subject, covering a 7 years range (2013-today), a period that accounts for more than 60% of the total number of publications in the topic in the main bibliographic databases and search engines. Focus was placed on the therapeutic fields of application, absorption and distribution processes and current efforts for the translation into the clinical practice of lipid-based nanoparticles. For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials.

Integrin α2β1-Targeted Self-Assembled Nanocarriers for Tumor Bioimaging.

Recent developments in near-infrared (NIR) dyes and imaging modalities enable tumor fluorescent images in preclinical and clinical settings. However, NIR dyes have several drawbacks, and therefore, there is an unmet diagnostic need for NIR dye encapsulation in appropriate pharmaceutical nanocarriers with targeting abilities for the purpose of achieving effective diagnosis and image-guided surgeries. Because integrin receptors are established diagnostic targets, the cyclic Arg-Gly-Asp (RGD) peptides, recognizing the αVβ3 integrin, have been extensively investigated for radiology and bioimaging of tumors. However, the Lys(Arg)-Thr-Ser [K(R)TS] cyclic peptides, selective for collagen receptors α1β1/α2β1 integrins, which are overexpressed in many tumors, were not yet investigated and therefore used here for tumor bioimaging with a unique α2β1-integrin-targeted nanocarrier, encapsulating the indocyanine green NIR dye. We synthesized three kinds of peptides: two cyclic RTS peptides functional only in the cyclic conformation and a linear peptide lacking the cyclic cysteine constrained RTS loop. We used them for the preparation of integrin-targeted self-assembled nanocarriers (ITNCs), referred to as OF5 and OF27, and a nontargeted control nanocarrier, referred to as OF70. Their selective association was demonstrated with α2β1 integrin expressing cell cultures and three-dimensional tumor spheroids and by competition with a α2β1 selective disintegrin. Cytotoxicity experiments in vitro demonstrated the safety of the ITNCs. The targeting potential and the biodistribution of the ITNCs, applied intravenously in A431 tumor-bearing nude mice, were evaluated in vivo using NIR bioimaging. Time-dependent biodistributions indicated that the ITNC OF27 showed higher fluorescent signals in main tissues, with no cytotoxic effects to major organs, and presented higher accumulation in tumors. Cumulatively, these results highlight the potential of the ITNC OF27 as an optical and innovative pharmaceutical bioimaging system, suitable for integrin α2β1 receptor in vivo tumor targeting and visualization in the NIR region.

Liposomes Loaded with the Proteasome Inhibitor Z-Leucinyl-Leucinyl-Norleucinal are Effective in Inducing Apoptosis in Colorectal Cancer Cell Lines.

Colorectal cancer (CRC) is one of the main causes of cancer-related death in developed countries. Targeted therapies and conventional chemotherapeutics have been developed to help treat this type of aggressive cancer. Among these, the monoclonal antibodies cetuximab (Cxm) and panitumumab specifically target and inactivate the signaling of ERBB1 (EGF receptor), a key player in the development and progression of this cancer. Unfortunately, these antibodies are effective only on a small fraction of patients due to primary or secondary/acquired resistance. However, as ERBB1 cell surface expression is often maintained in resistant tumors, ERBB1 can be exploited as a target to deliver other drugs. Liposomes and immunoliposomes are under intensive investigation as pharmaceutical nanocarriers and can be functionalized with specific antibodies. In this study, we first investigated the anti-cancer activity of a cell permeable tripeptide, leucine-leucin-norleucinal (LLNle), an inhibitor of gamma-secretase and proteasome, in three different CRC cell lines that express ERBB1. We formulated LLNle-liposomes and Cxm-conjugated LLNle-loaded liposomes (LLNle-immunoliposomes) and evaluated their efficacy in inhibiting cell survival. Despite similar pro-apoptotic effects of free LLNle and LLNle-liposomes, immunoliposomes-LLNle were significantly less effective than their unconjugated counterparts. Indeed, immunoliposomes-LLNle were readily internalized and trafficked to lysosomes, where LLNle was likely trapped and/or inactivated. In conclusion, we demonstrated that LLNle was readily delivered to CRC cell lines by liposomes, but immunoliposomes-LLNle failed to show significant anti-cancer activity.

Potential advancements of nanocarriers in topical drug delivery: a mini review

The topical route offers many attractive alternatives for the drug delivery as compared to oral administration and injection. Besides, skin provides a reservoir that delivers drug delivery for days. Nanotechnology, science at nano scale, has been emerged as a strong and potential discipline focusing on atom and molecular mechanisms that contributes to a diversity of applications in various fields such as controlled and targeted drug delivery, bio-imaging, agriculture, 3D printing, physics, mechanics, etc. Nanocarriers avoid local irritation and toxicity. The nanocarrier drug delivery system has emerged as interesting field that broaden up the use various drugs (lipophillic and hydrophilic) and provides ease of fabrication of formulations that can be efficiently delivered via topical route. The nanocarrier based delivery has been explored to deliver hydrophilic and lipophilic drug candidates through stratum corneum with local and systemic effects for the treatment of variety different skin diseases. Nanocarriers such as a nanoparticle, dendrimer, ethosome, and liposome are made up of polymers and material that differ in structure and chemical nature. These nanocarriers can deliver the drug at the target site and reduce side effects by lowering drug doses. This review covers all aspects of pharmaceutical nanocarriers related to their applications and recent advancements.