No abstract

Drug hydrolytic degradation, caused by atmospheric and inherent humidity, significantly reduces the therapeutic effect of pharmaceutical solid dosages. Moisture barrier film coating is one of the most appropriate and effective approaches to protect the active pharmaceutical ingredients (API) from hydrolytic degradation during the manufacturing process and storage. Coating formulation design and process control are the two most commonly used strategies to reduce water vapor permeability to achieve the moisture barrier function. The principles of formulation development include designing a coating formulation with non-hygroscopic/low water activity excipients, and formulating the film-forming polymers with the least amount of inherent moisture. The coating process involves spraying organic or aqueous coating solutions made of natural or synthetic polymers onto the surface of the dosage cores in a drum or a fluid bed coater. However, the aqueous coating process needs to be carefully controlled to prevent hydrolytic degradation of the drug due to the presence of water during the coating process. Recently, different strategies have been designed and developed to effectively decrease water vapor permeability and improve the moisture barrier function of the film. Those strategies include newly designed coating formulations containing polymers with optimized functionality of moisture barrier, and newly developed dry coating processes that eliminate the usage of organic solvent and water, and could potentially replace the current solvent and aqueous coatings. This review aims to summarize the recent advances and updates in moisture barrier coatings.

The synergistic influences of three unsaturated fatty acids (UFAs, namely linoleic acid, oleic acid and linolenic acid) on the fatty acid composition of Saccharomyces cerevisiae and major volatile compounds were investigated in synthetic grape juice. The addition of UFAs led to a corresponding increase in UFAs in the cellular lipid, which was accompanied by a reverse reduction in the content of medium-chain saturated fatty acids (C6:0 to C14:0) and little variation in that of long-chain saturated fatty acids (C16:0 to C24:0). The supplementation of UFAs considerably improved yeast growth and fermentation activity and, in particular, increased the concentrations of most volatile compounds in wine, including higher alcohols (2-phenylethanol, 2-methyl-1-propanol and 3-(methylthio)-1-propanol), medium-chain fatty acids (butanoic acid, hexanoic acid and octanoic acid), acetate esters (isoamyl acetate and 2-phenylethyl acetate) and all ethyl esters. Remarkable linear relationships were further found between ethyl esters and the concentration of the added UFAs (R 2 from 0.909 to 0.996), which significantly intensified the fruity, flowery and sweet attributes of the final wine, as assessed by calculating the odour activity values. Our results suggest that rationally increasing the concentration of UFAs is not only a practical method to improve yeast fermentation activity, but also a potential approach to manipulating wine aroma.

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation.

Locusta migratoria is a classic hemimetamorphosis insect and has caused widespread economic damage to crops as a migratory pest. Researches on the expression pattern of functional genes in L. migratoria have drawn focus in recent years, especially with the release of genome information. Real-time quantitative PCR is the most reproducible and sensitive approach for detecting transcript expression levels of target genes, but optimal internal standards are key factors for its accuracy and reliability. Therefore, it's necessary to provide a systematic stability assessment of internal control for well-performed tests of target gene expression profile. In this study, twelve candidate genes (Ach, Act, Cht2, EF1α, RPL32, Hsp70, Tub, RP49, SDH, GAPDH, 18S, and His) were analyzed with four statistical methods: the delta Ct approach, geNorm, Bestkeeper and NormFinder. The results from these analyses aimed to choose the best suitable reference gene across different experimental situations for gene profile study in L. migratoria. The result demonstrated that for different developmental stages, EF1α, Hsp70 and RPL32 exhibited the most stable expression status for all samples; EF1α and RPL32 were selected as the best reference genes for studies involving embryo and larvae stages, while SDH and RP49 were identified for adult stage. The best-ranked reference genes across different tissues are RPL32, Hsp70 and RP49. For abiotic treatments, the most appropriate genes we identified were as follows: Act and SDH for larvae subjected to different insecticides; RPL32 and Ach for larvae exposed to different temperature treatments; and Act and Ach for larvae suffering from starvation. The present report should facilitate future researches on gene expression in L. migratoria with accessibly optimal reference genes under different experimental contexts.

Micro/nanomotors are able to convert energy in different forms into propulsion and movement with predesigned directions and velocities, enabling them to be self‐propelled carriers and vehicles for the delivery of active pharmaceutical ingredients and other biomedical cargos to the target sites such as tumors. However, the inadequate energy and noncontrollable moving directions remain the grand challenges for their promising applications. Recently, an increasing attention has been paid to these issues and numerous reported researches have focused to design and develop more efficient and precisely controllable micro/nanomotors with different methods. This review aims to summarize those studies and to introduce newly developed micro/nanomotors including synthetic micro/nanomotors and biohybrid motors, discussing the control mechanisms as well as advantages and limitations thereof. Conclusions and future perspectives are also provided in brief.

BackgroundMatrix-metalloproteinases, which are overexpressed in many types of cancer, can be applied to improve the bioavailability of chemotherapeutic drugs and guide therapeutic targeting. Thus, we aimed to develop enzyme-responsive nanoparticles based on a functionalized copolymer (mPEG-Peptide-PCL), which was sensitive to matrix metalloproteinase, as smart drug vesicles for enhanced biological specificity and reduced side effects.ResultsThe rate of in vitro curcumin (Cur) release from Cur-P-NPs was not markedly accelerated in weakly acidic tumor microenvironment, indicating a stable intracellular concentration and a consistent therapeutic effect. Meanwhile, P-NPs and Cur-P-NPs displayed prominent biocompatibility, biostability, and inhibition efficiency in tumor cells. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, implying enhanced cell permeability and targeting ability. Moreover, the internalization and intracellular transport of Cur-P-NPs were mainly via macropinocytosis. Studies of pharmacodynamics and cellular uptake in vitro and biodistribution in vivo demonstrated that Cur-P-NPs had stronger target efficiency and therapeutic effect than Cur-DMSO and Cur-NPs in tumor tissue.ConclusionResults indicate that Cur-P-NPs can be employed for active targeted drug delivery in cancer treatment and other biomedical applications.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0384-8) contains supplementary material, which is available to authorized users.

Background: Specific targeting ability and good cell penetration are two critical requirements of tumor-targeted delivery systems. In the present work, we developed a novel matrix metalloprotein-triggered, cell-penetrating, peptide-modified, star-shaped nanoparticle (NP) based on a functionalized copolymer (MePEG-Peptide-Tri-CL), with the peptide composed of GPLGIAG (matrix metalloprotein-triggered peptide for targeted delivery) and r9 (cell-penetrating peptide for penetration improvement) to enhance its biological specificity and therapeutic effect. Results: Based on the in vitro release study, a sustained release profile was achieved for curcumin (Cur) release from the Cur-P-NPs at pH 7.4. Furthermore, the release rate of Cur was accelerated in the enzymatic reaction. MTT assay results indicated that the biocompatibility of polymer NPs (P-NPs) was inversely related to the NP concentration, while the efficiency toward tumor cell inhibition was positively related to the Cur-P-NP concentration. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, indicating improved penetration of tumor cells. An in vivo biodistribution study further demonstrated that Cur-P-NPs exhibited stronger targeting to A549 xenografts than to normal tissue. Furthermore, the strongest tumor growth inhibition (76.95%) was observed in Cur-P-NP-treated A549 tumor xenograft nude mice, with slight pulmonary toxicity. Conclusion: All results demonstrated that Cur-P-NP is a promising drug delivery system that possesses specific enzyme responsiveness for use in anti-tumor therapy.