The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time. For most drugs, sufficient in vivo circulation time is the ...basis of high bioavailability. Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system, to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect. The physical and chemical properties of drug carriers, such as size, shape, surface charge and surface modification, would affect their in vivo circulation time, metabolic behavior and biodistribution. The final circulation time of carriers is determined by the balance between macrophage recognitions, blood vessel penetration and urine excretion. Therefore, when designing the drug delivery system, we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually. This article mainly reviews the effect of carrier size, size, surface charge and surface properties on its circulation time in vivo, and discusses the mechanism of these properties affecting circulation time. This review has reference significance for the research of long-circulation drug delivery system.
The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties such as size, shape, surface charge and surface modification on their circulation time. And we discussed how these physicochemical properties allow the carrier to evade rapid recognition and clearance by the mononuclear phagocyte system.
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In recent years, nanocrystal technology has been extensively investigated. Due to the submicron particle size and unique physicochemical properties of nanocrystals, they overcome the problems of low ...drug solubility and poor bioavailability. Although the structures of nanocrystals are simple, the further development of these materials is hindered by their stability. Drug nanocrystals with particle sizes of 1∼1000 nm usually require the addition of stabilizers such as polymers or surfactants to enhance their stability. The stability of nanocrystal suspensions and the redispersibility of solid nanocrystal drugs are the key factors for the large-scale production of nanocrystal preparations. In this paper, the factors that affect the stability of drug nanocrystal preparations are discussed, and related methods for solving the stability problem are put forward.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Grain weight is the most important component of rice yield and is mainly determined by grain size, which is generally controlled by quantitative trait loci (QTLs). Although numerous QTLs that ...regulate grain weight have been identified, the genetic network that controls grain size remains unclear. Herein, we report the cloning and functional analysis of a dominant QTL, grain length and width 2 (GLW2), which positively regulates grain weight by simultaneously increasing grain length and width. The GLW2 locus encodes OsGRF4 (growth‐regulating factor 4) and is regulated by the microRNA miR396c in vivo. The mutation in OsGRF4 perturbs the OsmiR396 target regulation of OsGRF4, generating a larger grain size and enhanced grain yield. We also demonstrate that OsGIF1 (GRF‐interacting factors 1) directly interacts with OsGRF4, and increasing its expression improves grain size. Our results suggest that the miR396c‐OsGRF4‐OsGIF1 regulatory module plays an important role in grain size determination and holds implications for rice yield improvement.
In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in ...clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.
Purpose
Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D ...printed IDTs to improve palatability.
Methods
A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and
in vitro
drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results.
Results
The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation.
Conclusions
Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.
Bacillus thuringiensis (Bt) is an important biological insecticide used to management of different agricultural pests by producing toxic parasporal crystals proteins. Strain HD521 has an antagonistic ...effect against Rhizoctonia solani AG1IA, the causal agent of rice sheath blight. This strain with three cry7 genes can the formation of bipyramidal parasporal crystals (BPCs). BPCs are used for insecticidal activities against Henosepilachna vigintioctomaculata larva (Coleoptera). Strain HS18-1 contains different types of BPCs encoding genes and has effective toxicity for Lepidoptera and Diptera insects. Here we report the whole genome sequencing and assembly of HD521 and HS18-1 strains and analyzed the genome constitution covering virulence factors, types of plasmid, insertion sequences, and prophage sequences. The results showed that the genome of strain HD521 contains a circular chromosome and six circular plasmids, encoding eight types of virulence protein factors Immune Inhibitor A, Hemolytic Enterotoxin, S-layer protein, Phospholipase C, Zwittermicin A-resistance protein, Metalloprotease, Chitinase, and N-acyl homoserine lactonase (AiiA), four families of insertion sequence, and comprises six pro-phage sequences. The genome of strain HS18-1 contains one circular chromosome and nine circular plasmids, encoding five types of virulence protein factors Hemolytic Enterotoxin, S-layer protein, Phospholipase C, Chitinase, and N-acyl homoserine lactonase (AiiA) and four families of insertion sequence, and comprises of three pro-phage sequences. The obtained results will contribute to deeply understand the B. thuringiensis strain HD521 and HS18-1 at the genomic level.
Poly(d,l-lactide-co-glycolide) nanoparticles (PLGA-NP) have been extensively used as a drug delivery system for proteins and peptides. However, their negative surface charge decreases bioavailability ...under oral administration. Recently, cationically modified PLGA-NP has been introduced as novel carriers for oral delivery. The characteristics of the nanoparticles, such as particle size, surface charge, and bioadhesion are considered the most significant determinants of the effect of these nanoparticles both in vitro and in vivo. Our aim was to introduce and evaluate the physiochemical characteristics, bioadhesion, and biological activity of positively charged chitosan-coated PLGA-NP (CS-PLGA-NP), using insulin as a model drug. Results were compared to those of common negatively charged PLGA-NP and the in vitro cytotoxicity of the two types of nanoparticles was examined. These results indicate that both CS-PLGA-NP and PLGA-NP had a narrow size distribution, averaging less than 150nm. CS-PLGA-NP was positively charged (+43.1±0.3mV), exhibiting the cationic nature of chitosan, whereas PLGA-NP showed a negative surface charge (−1.72±0.2mV). CS-PLGA-NP exhibited stronger bioadhesive potency than PLGA-NP and much greater relative pharmacological availability with regard to orally delivered insulin. In addition, an evaluation of cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed no increase in toxicity in either kind of nanoparticle during the formulation process. The study proves that CS-PLGA-NP can be used as a vector in oral drug delivery systems for proteins and peptides due to its positive surface charge and bioadhesive properties.
Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent biocompatibility, ...biodegradability, non-toxicity, non-immunogenicity, and mechanical strength. PLAG are specifically used as microspheres for the sustained/controlled and targeted delivery of hydrophilic or hydrophobic drugs, as well as biological therapeutic macromolecules, including peptide and protein drugs. PLGAs with different molecular weights, lactic acid (LA)/glycolic acid (GA) ratios, and end groups exhibit unique release characteristics, which is beneficial for obtaining diverse therapeutic effects. This review aims to analyze the composition of PLGA microspheres, and understand the manufacturing process involved in their production, from a quality by design perspective. Additionally, the key factors affecting PLGA microsphere development are explored as well as the principles involved in the synthesis and degradation of PLGA and its interaction with active drugs. Further, the effects elicited by microcosmic conditions on PLGA macroscopic properties, are analyzed. These conditions include variations in the organic phase (organic solvent, PLGA, and drug concentration), continuous phase (emulsifying ability), emulsifying stage (organic phase and continuous phase interaction, homogenization parameters), and solidification process (relationship between solvent volatilization rate and curing conditions). The challenges in achieving consistency between batches during manufacturing are addressed, and continuous production is discussed as a potential solution. Finally, potential critical quality attributes are introduced, which may facilitate the optimization of process parameters.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Messenger RNA (mRNA) vaccines have shown great preventive potential in response to the novel coronavirus (COVID-19) pandemic. The lipid nanoparticle (LNP), as a non-viral vector with good safety and ...potency factors, is applied to mRNA delivery in the clinic. Among the recently FDA-approved SARS-CoV-2 mRNA vaccines, lipid-based nanoparticles have been shown to be well-suited to antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses. However, a design strategy for optimal mRNA-LNP vaccines has not been fully elaborated. In this review, we comprehensively and systematically discuss the research strategies for mRNA-LNP vaccines against COVID-19, including antigen and lipid carrier selection, vaccine preparation, quality control, and stability. Meanwhile, we also discuss the potential development directions for mRNA–LNP vaccines in the future. We also conduct an in-depth review of those technologies and scientific insights in regard to the mRNA-LNP field.
Thermosensitive hydrogels, having unique sol–gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This ...feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.
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