Bhushan S. Pattni,† Vladimir V. Chupin,‡ and Vladimir P. Torchilin*,†,§,∥ †Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, United States ‡Laboratory for Advanced Studies of Membrane Proteins, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

New Developments in Liposomal Drug Delivery.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

TFOS DEWS II Management and Therapy Report

Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

Particle size and physical state of the lipid phase are major factors influencing the permanence of lipid dispersions. Nanostructured lipid carriers (NLC) are a delivery system in which partial-crystallized lipid particles with mean radii ≤ 100 nm are dispersed in an aqueous phase containing emulsifier(s), as a potential delivery system may have some advantages in certain circumstances when compared with other colloidal carriers. NLC are a useful nutraceutical delivery system with high drug loading, encapsulation efficiency and stability. They may increase, bioavailability and stability of bioactive compounds, and shelf-life, consumer acceptability, functionality, nutritional value and safety of food systems, and provide controlled release of encapsulated materials. In this review, beneficial aspects of NLC are presented and valuable information about ingredients, production methods, structure and characteristics of them provided. Moreover, potential applications and disadvantages of NLC as emerging delivery system in food science are introduced. Industrial relevance With the increasing public perception of a strong correlation between food and disease prevention, producers are trying to enrich staple foods and beverages with nutraceuticals and produce functional foods. Nonetheless, fortification of aqueous-based food with many of nutraceuticals is greatly limited owing to their poor water-solubility, chemical instability, and low bioavailability. NLC are a novel nanocarrier that may dispel these limitations, combine the advantages of other lipid nanocarriers and avoid some of their disadvantages. They may be suitable for application within foods and transparent/opaque beverages.

Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules

Nanostructured lipid carriers: Promising drug delivery systems for future clinics.

Spherical and discoidal tanshinone IIA-loaded reconstituted high density lipoproteins (TA-rHDL) with different formulations and techniques were prepared and characterized The targeting mechanism was investigated using a foam cell model Pharmacokinetics of four TA-rHDL formulations with or without apolipoproteins (apos) after a single dose intravenous injection to rabbits has been studied The results showed that the sizes of spherical and discoidal TA-rHDL increased after coupling with apos from 5538 nm to 15726 nm, 6103 nm to 16619 nm, and zeta potential decreased from -292 mV to -354 mV, -52 mV to -1182 mV, respectively The results of circular dichroic spectroscopy indicated variations of apos in protein secondary structure after binding with lipids Phagocytosis tests demonstrated that the spherical TA-rHDL had a targeting effect for foam cells through the scavenger receptor-BI and CE-TG interchange with TG-rich lipoproteins pathway under cholesteryl ester transfer protein Discoidal TA-rHDL could reconstruct to spheres and target via a similar route as TA-rHDL spheres, showing a higher targeting efficiency In vivo experiments showed that areas under the plasma level-time curve (AUC) of TA increased as a function of spherical and discoidal rHDL, which were 4 and 13 times more than that of TA suspensions, respectively Spherical and discoidal TA-rHDL had long circulating times in blood with mean residence time (MRT) of 15874 and 18956h, respectively, compared to 1802h of TA suspensions, 14190h of spherical TA-rHDL without apos and 15071 of discoidal TA-rHDL without apos The distribution volume of spherical TA-rHDL was 2143 and 1552 times as that of discoidal TA-rHDL and TA suspensions, respectively In conclusion, TA-rHDL may be a long-circulating, healthy and potentially targeted carrier for delivering lipophilic cardiovascular drugs

Tanshinone IIA-loaded reconstituted high density lipoproteins: Atherosclerotic plaque targeting mechanism in a foam cell model and pharmacokinetics in rabbits.

Recombinant high-density lipoprotein (rHDL) displays a similar anti-atherosclerotic effect with native HDL and could also be served as a carrier of cardiovascular drug for atherosclerotic plaque targeting In our previous studies, rHDL has shown a more potent anti-atherosclerotic efficacy as compared to the other conventional nanoparticles with a payload of lovastatin (LS) Therefore, we hypothesized that a synergistic anti-atherosclerotic effect of the rHDL carrier and the encapsulated LS might exist In this study, the dose-effect relationships and the combined effect of the rHDL and LS were quantitatively evaluated in RAW 2647 macrophage cells using the median-effect analysis, in which the rHDL carrier was regarded as a drug combined Median-effect analysis suggested that rHDL and LS exerted a desirable synergistic inhibition on the oxLDL internalization at a ratio of 6:1 ( Dm,LS: Dm,rHDL) in RAW 2647 macrophage cells About 50% of the reduction on the intracellular lipid contents was found when RAW2647 cells were treated with LS-loaded rHDLs at their respective median-effect dose ( Dm) concentrations and a synergistic effect on the mediating cholesterol efflux was also observed, which verified the accuracy of the results obtained from the median-effect analysis The mechanism underlying the synergistic effect of the rHDL carrier and the drug might be attributed to their potent inhibitory effects on SR-A expression In conclusion, the median-effect analysis was proven to be a feasible method to quantitatively evaluate the synergistic effect of the biofunctional carrier and the drug encapsulated

Evaluation of the Combined Effect of Recombinant High-Density Lipoprotein Carrier and the Encapsulated Lovastatin in RAW264.7 Macrophage Cells Based on the Median-Effect Principle.

This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit® NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease® were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases.

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A novel multi-unit tablet for treating circadian rhythm diseases.

Cell-based therapeutics are very promising modalities to address many unmet medical needs, including genetic engineering, drug delivery, and regenerative medicine as well as bioimaging. To enhance the function and improve the efficacy of cell-based therapeutics, a variety of cell surface engineering strategies (genetic engineering and non-genetic engineering) are developed to modify the surface of cells or cell-based therapeutics with some therapeutic molecules, artificial receptors, and multifunctional nanomaterials. In comparison to complicated procedures and potential toxicities associated with genetic engineering, non-genetic engineering strategies have emerged as a powerful and compatible complement to traditional genetic engineering strategies for enhancing the function of cells or cell-based therapeutics. In this review, we will first briefly summarize key non-genetic methodologies including covalent chemical conjugation (surface reactive groups–direct conjugation, and enzymatically mediated and metabolically mediated indirect conjugation) and noncovalent physical bioconjugation (biotinylation, electrostatic interaction, and lipid membrane fusion as well as hydrophobic insertion), which have been developed to engineer the surface of cell-based therapeutics with various materials. Next, we will comprehensively highlight the latest advances in non-genetic cell membrane engineering surrounding different cells or cell-based therapeutics, including whole-cell-based therapeutics, cell membrane-derived therapeutics, and extracellular vesicles. Advances will be focused specifically on cells that are the most popular types in this field, including erythrocytes, platelets, cancer cells, leukocytes, stem cells, and bacteria. Finally, we will end with the challenges, future trends, and our perspectives of this relatively new and fast-developing research field.

https://www.mdpi.com/2073-4360/11/12/2017/pdf

Advances on Non-Genetic Cell Membrane Engineering for Biomedical Applications

https://doi.org/10.1016/j.bioactmat.2022.03.041

Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery

Jianping Liu

Papers

Tanshinone IIA-loaded reconstituted high density lipoproteins: Atherosclerotic plaque targeting mechanism in a foam cell model and pharmacokinetics in rabbits.

Evaluation of the Combined Effect of Recombinant High-Density Lipoprotein Carrier and the Encapsulated Lovastatin in RAW264.7 Macrophage Cells Based on the Median-Effect Principle.

A novel multi-unit tablet for treating circadian rhythm diseases.

Advances on Non-Genetic Cell Membrane Engineering for Biomedical Applications

Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery