Design Of Nanocarriers Research Articles

Isoginkgetin synergizes with doxorubicin for robust co-delivery to induce autophagic cell death in hepatocellular carcinoma

Doxorubicin (DOX) widely used in hepatocellular carcinoma (HCC) can induce serious side effects and drug resistance. Herein, we aimed to seek a strategy to improve the efficacy and reduce the side effects of DOX in HCC based on an autophagy inducer drug called isoginkgetin (ISO). The design of multifunctional nanocarriers based on hyaluronic acid-conjugated and manganese-doped mesoporous silica nanoparticles (HM) for the co-delivery of antitumor drugs against HCC provided an effective and promising antitumor strategy. Our results showed that HM@ISO@DOX could efficiently inhibit HCC cell proliferation through activating autophagy through AMPKa-ULK1 pathway. Moreover, intravenous injection of HM@ISO@DOX significantly suppressed HCC tumor progression in nude mouse HCC model. Collectively, our findings revealed an anti-HCC mechanism of HM@ISO@DOX through autophagy and provide an effective therapeutic strategy for HCC. Statement of significanceIn our study, we constructed a co-delivery system by loading ISO and DOX in the mesoporous channels of manganese-doped mesoporous silica nanoparticles, which could be further conjugated with hyaluronic acid to obtain HM@ISO@DOX. The nanocarriers had been demonstrated to be biodegradable under the acidic and reducing tumor microenvironment, as well as to possess the tumor targeting capability via the conjugated hyaluronic acid. In addition, HM@ISO@DOX enhanced the therapeutic efficacy against human HCC tumor through the combinatorial therapies of chemotherapeutics, Mn2+-mediated chemodynamic therapeutics and autophagic cell death, which might be achieved through AMPK-ULK1 signaling. This work revealed that such a nanomedicine exhibited superior tumor accumulation and antitumor efficiency against HCC with extremely low systemic toxicity in an autophagy-boosted manner.

Optimization of Lipid Nanoparticles by Response Surface Methodology to Improve the Ocular Delivery of Diosmin: Characterization and In-Vitro Anti-Inflammatory Assessment.

Diosmin is a flavonoid with a great variety of biological activities including antioxidant and anti-inflammatory ones. Its cytoprotective effect in retinal pigment epithelium cells under high glucose conditions makes it a potential support in the treatment of diabetic retinopathy. Despite its benefits, poor solubility in water reduces its potential for therapeutic use, making it the biggest biopharmaceutical challenge. The design of diosmin-loaded nanocarriers for topical ophthalmic application represents a novelty that has not been yet explored. For this purpose, the response surface methodology (RSM) was used to optimize nanostructured lipid carriers (NLCs), compatible for ocular administration, to encapsulate diosmin and improve its physicochemical issues. NLCs were prepared by a simple and scalable technique: a melt emulsification method followed by ultrasonication. The experimental design was composed of four independent variables (solid lipid concentration, liquid lipid concentration, surfactant concentration and type of solid lipid). The effect of the factors was assessed on NLC size and PDI (responses) by analysis of variance (ANOVA). The optimized formulation was selected according to the desirability function (0.993). Diosmin at two different concentrations (80 and 160 µM) was encapsulated into NLCs. Drug-loaded nanocarriers (D-NLCs) were subjected to a physicochemical and technological investigation revealing a mean particle size of 83.58 ± 0.77 nm and 82.21 ± 1.12 nm, respectively for the D-NLC formulation prepared with diosmin at the concentration of 80 µM or 160 µM, and a net negative surface charge (−18.5 ± 0.60 and −18.0 ± 1.18, respectively for the two batches). The formulations were analyzed in terms of pH (6.5), viscosity, and adjusted for osmolarity, making them more compatible with the ocular environment. Subsequently, stability studies were carried out to assess D-NLC behavior under different storage conditions up to 60 days, indicating a good stability of NLC samples at room temperature. In-vitro studies on ARPE-19 cells confirmed the cytocompatibility of NLCs with retinal epithelium. The effect of D-NLCs was also evaluated in-vitro on a model of retinal inflammation, demonstrating the cytoprotective effect of D-NLCs at various concentrations. RSM was found to be a reliable model to optimize NLCs for diosmin encapsulation.

Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors.

Cancer is a genetic mutation disease that seriously endangers the health and life of all human beings. As one of the most amazing academic achievements in the past decade, CRISPR/Cas9 technology has been sought after by many researchers due to its powerful gene editing capability. CRISPR/Cas9 technology shows great potential in oncology, and has become one of the most promising technologies for cancer genome-editing therapeutics. However, its efficiency and the safety issues of in vivo gene editing severely limit its widespread application. Therefore, developing a suitable delivery method for the CRISPR/Cas9 system is an urgent problem to be solved at present. Rapid advances in nanomedicine suggest nanoparticles could be a viable option. In this review, we summarize the latest research on the potential use of nanoparticle-based CRISPR/Cas9 systems in cancer therapeutics, in order to further their clinical application. We hope that this review will provide a novel insight into the CRISPR/Cas9 system and offer guidance for nanocarrier designs that will enable its use in cancer clinical applications.

L-buthionine sulfoximine encapsulated hollow calcium peroxide as a chloroperoxidase nanocarrier for enhanced enzyme dynamic therapy

The appropriate design of multifunctional nanocarriers for chloroperoxidase (CPO) delivery and the simultaneous improvement of the efficiency of enzyme dynamic therapy (EDT) remain significant challenges. Herein, we report a facile one-step route to obtain a multifunctional nanocarrier for the formation of sodium hyaluronate-modified hollow calcium peroxide spheres with encapsulated L-buthionine sulfoximine (BSO), followed by delivery of CPO for enhanced EDT. After effective accumulation at the tumor sites, the nanocomposite rapidly decomposes and releases Ca2+, BSO molecules, CPO, and concurrently generates a large volume of hydrogen peroxide (H2O2) in the endogenous tumor microenvironment (TME). BSO molecules inhibit the biosynthesis of glutathione (GSH) by inactivating γ-glutamyl cysteine synthetase. Due to BSO-induced GSH depletion and self-supply of H2O2, the EDT efficiency of CPO was significantly enhanced to achieve high tumor therapy efficiency. Additionally, overloaded Ca2+ caused mitochondrial damage and amplified the oxidative stress. Moreover, calcification resulted from the unbalanced calcium transport channel caused by enhanced oxidative stress, accelerating tumor apoptosis and improving the efficacy of computed tomography (CT) imaging visual tumor therapy. This simple and efficient design for multifunctional nanocomposites will likely take an important place in the field of combined tumor therapeutics.

Influence of protein corona on the interaction of glycogen-siRNA constructs with ex vivo human blood immune cells.

Glycogen-nucleic acid constructs i.e., glycoplexes are emerging promising platforms for the alteration of gene expression and transcription. Understanding the interaction of glycoplexes with human blood components, such as serum proteins and peripheral blood mononuclear cells (PBMCs), is important to overcome immune cell activation and control biodistribution upon administration of the glycoplexes in vivo. Herein, we investigated the interactions of polyethylene glycol (PEG)ylated and non-PEGylated glycoplexes carrying siRNA molecules with PBMCs isolated from the blood of healthy donors. We found that both types of glycoplexes were non-toxic and were primarily phagocytosed by monocytes without triggering a pro-inflammatory interleukin 6 cytokine production. Furthermore, we investigated the role of the protein corona on controlling the internalization efficiency in immune cells - we found that the adsorption of serum proteins, in particular haptoglobin, alpha-1-antitrypsin and apolipoprotein A-II, onto the non-PEGylated glycoplexes, significantly reduced the uptake of the glycoplexes by PBMCs. Moreover, the non-PEGylated glycoplexes were efficient in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) knockdown in monocytic THP-1 cell line. This study provides an insight into the rational design of glycogen-based nanocarriers for the safe delivery of siRNA without eliciting unwanted immune cell activation and efficient siRNA activity upon its delivery.

The recent progress of inorganic‐based intelligent responsive nanoplatform for tumor theranostics

AbstractInorganic nanoplatform exhibits great potentials in drug delivery and responsive release attributed to its inherent physicochemical properties, good biocompatibility, surface modification, and easy synthesis. In this review, the recent progresses on the inorganic smart bio‐responsive nanoplatforms for tumor theranostics are summarized, which could be triggered by either endogenous tumor microenvironment (TME) or the exogenous physical and hopeful to achieve safe, precise, and high efficacy for tumor therapy. Notably, these nanoplatforms generally are dependent on the intelligent and multifunctional design of nanocarriers, including mesoporous silica nanoparticles (MSNs), black phosphorus (BP), Prussian blue (PB), and other inorganic‐based nanoparticles. Finally, the perspectives and challenges of inorganic nanoplatform in the future translational medicine are proposed.

New advances in pharmaceutical strategies for sensitizing anti-PD-1 immunotherapy and clinical research.

Attempts have been made continuously to use nano-drug delivery system (NDDS) to improve the effect of antitumor therapy. In recent years, especially in the application of immunotherapy represented by antiprogrammed death receptor 1 (anti-PD-1), it has been vigorously developed. Nanodelivery systems are significantly superior in a number of aspects including increasing the solubility of insoluble drugs, enhancing their targeting ability, prolonging their half-life, and reducing side effects. It can not only directly improve the efficacy of anti-PD-1 immunotherapy, but also indirectly enhance the antineoplastic efficacy of immunotherapy by boosting the effectiveness of therapeutic modalities such as chemotherapy, radiotherapy, photothermal, and photodynamic therapy (PTT/PDT). Here, we summarize the studies published in recent years on the use of nanotechnology in pharmaceutics to improve the efficacy of anti-PD-1 antibodies, analyze their characteristics and shortcomings, and combine with the current clinical research on anti-PD-1 antibodies to provide a reference for the design of future nanocarriers, so as to further expand the clinical application prospects of NDDSs. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Kappa Carrageenan/PEG-halloysite nanocomposites: Surface characterization with an artificial intelligence technique, antimicrobial, and anticancer properties

Within the field of pharmaceutical technology, the design of green and multifunctional nanocarriers has received significant attention due to their excellent synergistic anticancer and antimicrobial properties. In this study, a novel kappa carrageenan/polyethylene glycol-halloysite nanocomposite (κCA-PEG-Hal NC) was prepared as a part of the development of the cisplatin (Cis) delivery nanosystem in pancreatic cancer treatment. The prepared nanostructure was characterized by SEM, TEM, XRD, and FTIR techniques. The spherical κCA-PEG-Hal NC was outperformed by a smaller particle size of 65 ± 1 nm. The prepared nanostructure exhibited a high Cis release percentage of 90.44 ± 0.5%. The experimental results showed that the prepared κCA-PEG-Hal NC had a high cytotoxic effect on HepG2 hepatocellular carcinoma and MIA PaCa-2 pancreatic cancer cells, while having low cytotoxicity against HUVEC human umbilical vein endothelial cells. Furthermore, the κCA-PEG-Hal NC had robust antimicrobial effects against different pathogenic microorganisms. Due to the multifunctional nature of κCA-PEG-Hal NC, it is proposed as an effective nanocarrier for delivery of anticancer drug (Cis) and an antimicrobial agent with excellent surface and biological properties.

Lipoplexes for effective in vitro delivery of microRNAs to adult human cardiac fibroblasts for perspective direct cardiac cell reprogramming

Design of nanocarriers for efficient miRNA delivery can significantly improve miRNA-based therapies. Lipoplexes based on helper lipid, dioleoyl phosphatidylethanolamine (DOPE) and cationic lipid [2-(2,3-didodecyloxypropyl)-hydroxyethyl] ammonium bromide (DE) were formulated to efficiently deliver miR-1 or a combination of four microRNAs (miRcombo) to adult human cardiac fibroblasts (AHCFs). Lipoplexes with amino-to-phosphate groups ratio of 3 (N/P 3) showed nanometric hydrodynamic size (372 nm), positive Z-potential (40 mV) and high stability under storage conditions. Compared to commercial DharmaFECT1 (DF), DE-DOPE/miRNA lipoplexes showed superior miRNA loading efficiency (99 % vs. 64 %), and faster miRNA release (99 % vs. 82 % at 48 h). DE-DOPE/miR-1 lipoplexes showed superior viability (80–100 % vs. 50 %) in AHCFs, a 2-fold higher miR-1 expression and Twinfilin-1 (TWF-1) mRNA downregulation. DE-DOPE/miRcombo lipoplexes significantly enhanced AHCFs reprogramming into induced cardiomyocytes (iCMs), as shown by increased expression of CM markers compared to DF/miRcombo.

Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions.

DNA nanostructure-based responsive drug delivery has become an increasingly potent method in cancer therapy. However, a variety of important cancer biomarkers have not been explored in searching of new and efficient targeted delivery systems. Uracil degradation glycosylase and human apurinic/apyrimidinic endonuclease are significantly more active in cancer cells. Here, we developed uracil-modified DNA nanotubes that can deliver drugs to tumor cells through an enzyme-induced disassembly process. Although the reaction of these enzymes on their natural DNA substrates has been established, their reactivity on self-assembled nanostructures of nucleic acids is not well understood. We leveraged molecular dynamic simulation based on coarse-grained model to forecast the enzyme reactivity on different DNA designs. The experimental data are highly consistent with the simulation results. It is the first example of molecule simulation being used to guide the design of enzyme-responsive DNA nano-delivery systems. Importantly, we found that the efficiency of drug release from the nanotubes can be regulated by tuning the positions of uracil modification. The DNA nanotubes equipped with cancer-specific aptamer AS1411 are used to deliver doxorubicin to tumor-bearing mice not only effectively inhibiting tumor growth but also protecting major organs from drug-caused damage. We believe that this work provides new knowledge on and insights into future design of enzyme-responsive DNA-based nanocarriers for drug delivery.

Abstract 5073: A novel in-situ nanoparticle self-assembly for combination delivery of therapeutics to non-small cell lung cancer

Abstract Background: Lung cancer is a predominant cause of morbidity and mortality across the world. Among all types of cancers, lung cancer is the leading cause of cancer mortalities in the United States. Non-small cell lung cancer is one of the dominant divisions of lung cancer that solely represents 85-90% of all lung cancer cases. Up to the present time, primary treatment regimens for this cancer include radiation therapy, chemotherapy, and surgery, with chemotherapy being the best option thus far. Despite the eminent benefits of chemotherapy, its value is offset by severe side effects such as renal and/or hepatic toxicity or insufficient amounts of drug available at the target site. Such pitfalls can be handled by employing natural compounds (polyphenols, phytochemicals, xanthonoid, etc.,) as chemopreventives or chemosensitizers which can improve chemotherapy activity while reducing its systemic side effects and drug resistance. To this end, our recent efforts demonstrated a synergistic therapeutic benefit of gambogic acid (GA) and gemcitabine (Gem) against lung cancer. However, simultaneous delivery of these two drugs at the tumor site is highly challenging. Therefore, development of an injectable nanoformulation that can effectively deliver both hydrophobic (GA) and hydrophilic (Gem) drugs in one formulation is a clinically unmet need. Methods: Pursuing the novel nanotherapy approach, our lab has developed an in-situ biodegradable and biocompatible human serum albumin (HSA) and tannic acid (TA) mediated complexed GA and Gem nanoparticles (G-G@HTA NPs) using the solvent evaporation method. G-G@HTA NPs formation was confirmed by particle size, FT-IR, and H-NMR. A superior therapeutic activity of G-G@HTA NPs was demonstrated by multiple in vitro functional assays as well as in an animal mouse model. Results: Our results confirmed that G-G@HTA NPs have the ideal particle size and surface charge for cancer cell/tissue delivery which can clearly be evident by preferential uptake of these nanoparticles in lung cancer cells. Further, G-G@HTA NPs superiorly inhibited cell proliferation and clonogenicity of NSCLC cells. Additionally, G-G@HTA NPs revealed an obvious and precise targeting of tumors in vivo. The promoted and more synergistic anti-tumor efficacy of G-G@HTA NPs was attained than that of combined treatments and single drugs treatments. These events were resulted with no apparent systemic and organ toxicities. Conclusion: In summary, this study details the design of a novel nanocarrier and provides an optimized strategy for constructing dual-loaded nanoparticles using a biodegradable, non-toxic, human serum albumin-tannic acid-based platform for GA and Gem co-delivery in the treatment of NSCLC which confirms a strong feasibility to implement such synergistic nanomedicine regimen in pre-clinical and clinical translations in future. Citation Format: Elham Hatami, Prashanth K. Nagesh, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu. A novel in-situ nanoparticle self-assembly for combination delivery of therapeutics to non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5073.

Perfluorocarbon Nanodroplets for Dual Delivery with Ultrasound/GSH-Responsive Release of Model Drug and Passive Release of Nitric Oxide.

Nitric oxide (NO) plays a critical role as an important signaling molecule for a variety of biological functions, particularly inhibiting cell proliferation or killing target pathogens. To deliver active radical NO gaseous molecule whose half-life is a few seconds in a stable state, the design and development of effective exogenous NO supply nanocarriers are essential. Additionally, the delivery of desired drugs with NO can produce synergistic effects. Herein, we report a new approach that allows for the fabrication of dual ultrasound (US)/glutathione (GSH)-responsive perfluorocarbon (PFC) nanodroplets for the controlled release of model drug and passive release of safely incorporated NO. The approach centers on the synthesis of a disulfide-labeled amphiphilic block copolymer and its use as a GSH-degradable macromolecular emulsifier for oil-in-water emulsification process of PFC. The fabricated PFC nanodroplets are colloidally stable and enable the encapsulation of both NO and model drugs. Encapsulated drug molecules are synergistically released when ultrasound and GSH are presented, while NO molecules are passively but rapidly released. Our preliminary results demonstrate that the approach is versatile and can be extended to not only GSH-responsive but also other stimuli-responsive block copolymers, thereby allowing for the fabrication of broad choices of stimuli-responsive (smart) PFC-nanodroplets in aqueous solution for dual delivery of drug and NO therapeutics.

The influence of a biomimetic pulmonary surfactant modification on the in vivo fate of nanoparticles in the lung

Direct biomimetic modification of nanoparticles (NPs) with endogenous surfactants is helpful to improve the biocompatibility of NPs and avoid damage to the physiological function of the lung. Therefore, the objective of this study is to investigate the influence of biomimetic endogenous pulmonary surfactant phospholipid modification on the in vivo fate of NPs after lung delivery. Here, two neutral phospholipids (dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylamine (DPPE)) and two negatively charged phospholipids (dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylserine (DPPS)) were selected to modify paclitaxel (PTX)-loaded PLGA NPs with different molar ratio. DPPC, DPPE, and DPPG improved mucoadhesion, in contrast, DPPS improved the mucus permeability of the NPs. Neutral DPPC and DPPE reduced, but negatively charged DPPS and DPPG increased the uptake by alveolar macrophages, all types of phospholipid increased the uptake by lung epithelial cells and increased PTX retention in the whole lung. Whereas, DPPC, DPPE, and DPPG promoted PTX retention in bronchoalveolar lavage fluid (BALF), while DPPS promoted PTX absorption in the lung tissue. Only DPPS-PLGA (1:1) NPs remarkably increased PTX systemic exposure. A good correlation between PTX percentage in the supernatant of BALF and PTX concentration in plasma was established, implying PTX entered the system circulation mainly in molecular form. Phospholipid modification had no effect on extrapulmonary organ distribution of PTX. Taken together, our study disclosed that different phospholipid modification can endow the NPs mucoadhesive or mucus penetration and cellular uptake properties, with tunable retention in BALF and absorption in the lung tissue, providing the scientific background for translational nanocarrier design for inhalation as required. Statement of significanceInhaled nanomedicines will inevitably interact with pulmonary surfactant and form “surfactant corona”. However, the contribution of individual pulmonary surfactant phospholipid on the in vivo fate of nanomedicines is still unclear. In this regard, the most abundant pulmonary surfactant phospholipid dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylamine, and dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylserine were selected to modify the paclitaxel loaded PLGA nanoparticles and the effect of these pulmonary surfactant phospholipids on their in vivo fate was investigated. It was demonstrated that different phospholipid modification can endow the nanoparticles mucoadhesive or mucus penetration properties, with tunable retention in bronchoalveolar lavage fluid, alveolar macrophages uptake and absorption in the lung tissue. The present study provided a comprehensive understanding for the role of pulmonary surfactant phospholipid on inhaled nanomedicines.

Role of nanomaterials with special reference to pharmaceutical technology

Nanocarriers have emerged as a safe and effective method of medication administration and release during the past few years. When compared to their larger-scale counterparts, nanoparticles display amazing properties. The excellent biocompatibility of many of these carriers makes them more attractive, as does the fact that they provide better effectiveness, particularly in cancer therapies. Over the past half-century, nanocrystal, liposomal, and micelle nanocarriers for drug administration and release have been widely studied. As a result of these successful uses, the pharmaceutical industry now has a whole new product to choose from. An overview of recent works on nanocarrier materials and designs to improve the efficacy of medications for illness treatment is provided below. As organic and inorganic nanocarrier materials that are highly biocompatible and easy to manipulate get the most interest, specific emphasis is paid to the design and implementation of novel nanocarrier materials such as nanohydrogels, chitins, graphene oxides, and solid lipoprotein nanoparticles. Each summary shows how far the project has progressed. In order to give better therapy to patients, there is a pressing demand in pharmaceutical technology for improved knowledge of the current condition of these nanomaterials.

Design of silica nanocarriers: Tuning the release to embryonic stem cells by simple strategies

The design of mesoporous silica nanoparticles (MSNs) for drug delivery is attracting increasing interest. Controlled release of their cargo is usually mediated by diffusion and erosion mechanisms, which might not reach the expected therapeutic effects. Here, we report the development and characterization of MSNs which modulate the cargo release in different cell models: fibroblasts and embryonic stem cells. Based on a double strategy: the presence of multimodal pore channels and a chitosan coating, we demonstrated a modulated release. Our results show that MSNs could be used for controlled drug delivery in different cell types, showing the potential of improving pluripotent stem cells differentiation and reprogramming protocols with promising applications in biomedicine.

Pore architecture influences the enzyme immobilization performance of mesoporous silica nanospheres

Immobilized enzymes on silica nano-carriers are stable biocatalysts with the potential for use in a plethora of applications. Studying how the structural characteristics of silica nano-carriers influence the performance of immobilized enzymes allows for the optimization of performance. This work investigates the influence of the pore architecture of silica nanospheres on enzyme loading, release, and reusability. Compared to dendritic mesoporous silica nanospheres (DMSN) with funnel-shaped wide-open pores, fractal silica nanoparticles (FSN) have a far more complex pore structure. FSN showed significantly higher immobilization capacity, sustained release, and enhanced reusability towards two model enzymes. The knowledge gained from this work paves the way for the rational design of enzyme nano-carriers for various applications.

Self-assembled dehydropeptide nanocarrier as a delivery system for antitumor drug temozolomide

Stable molecular conformation and intermolecular forces are essential for peptide self-assembly. In this study, one novel dehydropeptide (DDP) monomer (Boc-(Z)Cα,β-ΔPhe-Gly-NHMe, DDP 1) was prepared; its conformation was confirmed to be more stable than the normal peptide 2 by nuclear magnetic resonance (NMR) and X-ray crystal diffraction experiments. DDP 1 was self-assembled to one novel dehydropeptide nanomaterial (DDPN 1). Fourier transform infrared (FTIR) spectroscopy results showed that hydrogen bonding was the main driving force of self-assembly. Electron microscope images displayed that the DDPN 1 fibers were longer and more stable than peptide 2 nanomaterials. Results of cell activity and enzyme hydrolysis proved that DDPN 1 had excellent biocompatibility and resistance to the enzymatic hydrolysis of protease K. Therefore, the DDPN 1 was used to load the antitumor drug temozolomide (TMZ). Due to intermolecular hydrogen bonds formed between TMZ and DDPN 1, TMZ-loaded DDPN 1 had a high percent entrapment efficiency (EE) of 83.72 ± 4.30% (n = 8) and a percent drug loading efficiency (LE) of 6.70 ± 0.34% (n = 8), and the half-life of TMZ-loaded DDPN 1 was 2.5–3 times longer than that of TMZ at pH 7. The in vitro cell viability results revealed that TMZ-loaded DDPN 1 exhibited higher antitumor activity (IC50 = 552.1 μM) against U118-MG than that of TMZ (IC50 = 1980.1 μM), possibly because that U118-MG cells uptook more TMZ from TMZ-loaded DDPN 1 than from free TMZ directly. This study is expected to inspire the design of biocompatible nanocarriers applied for anti-enzymatic hydrolysis in drug delivery systems.

What's Next after Lipid Nanoparticles? A Perspective on Enablers of Nucleic Acid Therapeutics.

Recent success of mRNA-based COVID-19 vaccines have bolstered the strength of nucleic acids as a therapeutic platform. The number of new clinical trial candidates is skyrocketing with the potential to address many unmet clinical needs. Despite advancements in other aspects, the systemic delivery of nucleic acids to target sites remains a major challenge. Thus, nucleic acid based therapy has yet to reach its full potential. In this review, we shed light on a select few prospective technologies that exhibit substantial potential over traditional nanocarrier designs for nucleic acid delivery. We critically analyze these systems with specific attention to the possibilities for clinical translation.

Design and characterization of whey protein nanocarriers for thyme essential oil encapsulation obtained by freeze-drying

Innovative coating powders, based on whey protein concentrate (10–15 wt%) as native (WPC) or denatured protein (d-WPC), solely or in combination with alginate (0.75 wt%, AL), containing thyme essential oil, were produced using the freeze-drying technique. The impact of individual components (protein, alginate and oil) as well as the effect of heat-induced protein denaturation, was resolved regarding physicochemical, thermal and morphological properties of powders. High product yield (∼100%), particle size (223–257 nm), low moisture content (0.10–0.13%) and zeta potential (−19 to −25.6 mV) were determined for all samples. Strong antimicrobial activity of thyme oil nanocarriers against foodborne pathogens was demonstrated. Thermogravimetric analysis (TGA) indicated enhanced thermal stability of encapsulated oil. The most specific bands of structural compounds were identified in Raman spectra of the tested formulations, but principal component analysis (PCA) on recorded spectra was necessary to show the differences between carriers of different wall materials.

Design and physicochemical characterization of novel hybrid SLN-liposome nanocarriers for the smart co-delivery of two antitubercular drugs

In the present work a novel hybrid system for the delivery of two first-line antitubercular drugs, rifampicin (RIF) and isoniazid (INH), was designed. In order to control the release of the drugs and improve the efficiency of conventional carriers, like liposomes or solid lipid nanoparticles (SLNs), the new systems were developed by embedding SLNs into lecithin-based liposomes through the reverse-phase evaporation method. The hybrid system was characterized and compared to SLNs and liposomes in terms of size, encapsulation efficiency, morphology, and drug release. Detailed structural data and further evidence of the successful formation of the hybrid nanoparticles were obtained by applying small-angle neutron scattering (SANS). The hybrid system displayed a particle size comparable to liposomes and a high encapsulation efficiency. Morphological results obtained by atomic force microscopy (AFM) highlighted the possible presence of SLNs into the phospholipid bilayer; this hypothesis was supported by the slower in vitro release of the hydrophilic drug INH compared to liposomes and SLNs. Moreover, scattering differences of the inner core of the nanoparticles, evidenced in the SANS analysis, further corroborated the successful formation of the hybrid carrier. These novel systems were able to release their content as expected from an efficient dosage form in a perspective of an inhaled administration, improving the stability and the drug release profile with respect to plain liposomes. The physicochemical characterization of our systems opens new avenues towards a better understanding of the formulation of vesicles encapsulating SLNs.