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1.
Mechanistic Modeling of Wet Stirred Media Milling for Production of Drug Nanosuspensions.
Bilgili, E, Guner, G
AAPS PharmSciTech. 2020;(1):2
Abstract
Drug nanocrystals have been used for a wide range of drug delivery platforms in the pharmaceutical industry, especially for bioavailability enhancement of poorly water-soluble drugs. Wet stirred media milling (WSMM) is the most widely used process for producing dense, stable suspensions of drug nanoparticles, also referred to as nanosuspensions. Despite a plethora of review papers on the production and applications of drug nanosuspensions, modeling of WSMM has not been thoroughly covered in any review paper before. The aim of this review paper is to briefly expose the pharmaceutical scientists and engineers to various modeling approaches, mostly mechanistic, including computational fluid dynamics (CFD), discrete element method (DEM), population balance modeling (PBM), coupled methods, the stress intensity-number model (SI-SN model), and the microhydrodynamic (MHD) model with a main focus on the MHD model for studying the WSMM process. A total of 71 studies, 30 on drugs and 41 on other materials, were reviewed. Analysis of the pharmaceutics literature reveals that WSMM modeling is largely based on empirical, statistically based modeling approaches, and mechanistic modeling could help pharmaceutical engineers develop a fundamental process understanding. After a review of the salient features and various pros-cons of each modeling approach, recent advances in microhydrodynamic modeling and process insights gained therefrom were highlighted. The SI-SN and MHD models were analyzed and critiqued objectively. Finally, the review points out potential research directions such as more mechanistic and accurate CFD-DEM-PBM simulations and the coupling of the MHD-PBM models with the CFD.
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2.
Iron based nanotherapeutics for ferroptosis-induced cancer therapy.
Liu, YM, Chen, YH, Jin, YC, Tang, KZ
European review for medical and pharmacological sciences. 2020;(21):11323-11333
Abstract
Traditional anti-cancer treatments are far from satisfactory. There is an urgent to combine new therapeutics with traditional treatments to improve anti-cancer effectiveness. Ferroptosis is a new type of iron dependent non-apoptotic cell death could still offer benefits to patients who failed in apoptosis and necroptosis induction treatment. Iron plays a vital role during ferroptosis induction. While iron is a double-edged sword in cancer treatment, tumor specific distribution of iron is especially important. Nanotechnology is an efficient way to help drugs targeting distribution. We intended to review the latest progress in ferroptosis and iron based nanotherapeutics. First, the relationship between ferroptosis and iron metabolism was reviewed briefly to demonstrate the central role of iron in ferroptosis induction. Second, the latest progress of iron-based nanotechnology was presented and discussed according to the different designs. Finally, the future expectations of iron based nanotherapeutics for ferroptosis were spotlighted.
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3.
Dopamine-Decorated TiO2 Nanoparticles in Water: A QM/MM vs an MM Description.
Siani, P, Motta, S, Ferraro, L, Dohn, AO, Di Valentin, C
Journal of chemical theory and computation. 2020;(10):6560-6574
Abstract
Nanoparticle functionalization is a modern strategy in nanotechnology to build up devices for several applications. Modeling fully decorated metal oxide nanoparticles of realistic size (few nanometers) in an aqueous environment is a challenging task. In this work, we present a case study relevant for solar-light exploitation and for biomedical applications, i.e., a dopamine-functionalized TiO2 nanoparticle (1700 atoms) in bulk water, for which we have performed an extensive comparative investigation with both MM and QM/MM approaches of the structural properties and of the conformational dynamics. We have used a combined multiscale protocol for a more efficient exploration of the complex conformational space. On the basis of the results of this study and of some QM and experimental data, we have defined strengths and limitations of the existing force field parameters. Our findings will be useful for an improved modeling and simulation of many other similar hybrid bioinorganic nanosystems in an aqueous environment that are pivotal in a broad range of nanotechnological applications.
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4.
Research advances in preparation and application of chitosan nanofluorescent probes.
Liu, P, Wang, R, Su, W, Qian, C, Li, X, Gao, L, Jiao, T
International journal of biological macromolecules. 2020;:1884-1896
Abstract
Nanofluorescent material is developing rapidly as a new type of material. Nanofluorescent probes have broad application prospects in biological analysis, drug metabolism, and semiconductor optical materials. Chitosan is non-toxic and rich in nature which has good biocompatibility, and it can be combined with fluorescent probes. Therefore, the preparation and application of Nanofluorescent probes using chitosan as a carrier is summarized in this article. Fluorescent probes can be combined with other different materials through different reaction mechanisms, and the prepared composite materials can be widely used in biomaterials, sewage treatment, medicine and other fields.
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5.
Gelatin nanoparticles for NSAID systemic administration: Quality by design and artificial neural networks implementation.
Koletti, AE, Tsarouchi, E, Kapourani, A, Kontogiannopoulos, KN, Assimopoulou, AN, Barmpalexis, P
International journal of pharmaceutics. 2020;:119118
Abstract
The present study evaluates the preparation of systemic administrated NSAID gelatin nanoparticles with the aid of quality by design and artificial neural networks (ANNs). Specifically, two different preparation techniques (i.e. nanoprecipitation and two-step desolvation) were implemented for the formulation of diclofenac sodium (DLC) gelatin nanoparticles (GNs). Preliminary screening experiments showed that in the case of nanoprecipitation the best compromise (in terms of achieving both small particle size and high encapsulation efficiency) was the use of poloxamer 407 (as stabilizer) and acetone (as non-solvent), while in the case of two-step desolvation significant effect had the use of acetone, gelatin type and bloom number (type B with bloom 150 was selected for further evaluation). Implementation of a central composite experimental design (CCD), showed that in the case of nanoprecipitation the optimum formulation can be achieved at high poloxamer, high gelatin and moderate to high glutaraldehyde (GTA used for crosslinking) concentrations, while in the case of two-step desolvation high gelatin and GTA concentrations are needed. Artificial neural networks (ANN) implementation showed significantly improved prediction ability compared to MLR, while verification experiments showed good agreement between the ANN predicted and the experimentally obtained results. SEM analysis of the optimum suggested formulations showed nanoparticles with smooth surface, while powder X-ray diffraction (XRD) analysis showed the formation of amorphously dispersed systems, and Fourier transform infrared spectroscopy (FTIR) revealed the presence of molecular interactions irrespectively of the preparation method followed. A slightly faster release profile was observed in the case of nanoprecipitation based GNs, while all formulations followed biphasic release profile.
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6.
Chitosan nanoparticles as edible surface coating agent to preserve the fresh-cut bell pepper (Capsicum annuum L. var. grossum (L.) Sendt).
Hu, X, Saravanakumar, K, Sathiyaseelan, A, Wang, MH
International journal of biological macromolecules. 2020;(Pt A):948-957
Abstract
This work synthesized chitosan nanoparticles (CSNPs) by ionic gelation method using sodium tripolyphosphate pentabasic (STPP) and applied as nano-coating agent to extend the shelf life of fresh cut bell pepper (FCP) by preventing the microbial contaminations. The CSNPs were spherical shaped and 22.55 ± 1.69 d.nm sized with ζ-potential of 45.10 ± 1.42 mV confirmed by UHR-SEM, FE-TEM, and ζ-potential size analyses. The crystallinity and functional group changes were determined by XRD and FT-IR analyses respectivelly. The antioxidant activity of CSNPs was determined in terms of DPPH and ABTS scavenging activities. The 1% and 3% of CSNPs were found to be minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) respectively against all tested bacteria. The MBC of CSNPs was exhibited the promising anti-biofilm activity. Therefore, the 3% of CSNPs was used to prepare the chitosan nano-coating (CSNC), and applied on surface of FCP to prevent the microbial contaminations such as fungi, bacteria including Listeria monocytogenes and Salmonella enterica. The experimental results showed that the application of CSNC was maintained the FCP for 12 days at 5 °C without loss of weight, and sensory quality.
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7.
Experimental design in formulation optimization of vitamin K1 oxide-loaded nanoliposomes for skin delivery.
Samadi, N, Aberoomand Azar, P, Waqif Husain, S, Maibach, HI, Nafisi, S
International journal of pharmaceutics. 2020;:119136
Abstract
Due to the vitamin K1 sensitizing potential, the oxidized-isoform of vitamin K1 (vitamin K1 oxide, VKO), has been recently used for treating laser-induced purpura and hyperpigmentation in cosmetics. The objective of this study was to formulate VKO in nanoliposomes by using Box-Behnken experimental design to obtain an optimized formula with higher efficiency. The ratio of phospholipid to cholesterol (PC/CHO ratio), VKO concentration and sonication time in low, medium, and high levels were independent variables, while the percent of VKO entrapment efficiency (EE%) and vesicle size were selected as dependent variables. Optimum desirability was identified and an optimized formulation was prepared, characterized, and selected for in vitro VKO release and ex vivo skin permeation. The PC/CHO ratio showed the greatest effect on both responses (P < 0.0001). This effect was positive on EE%, while a negative effect was shown on vesicle size. The optimized formulation showed controlled drug release of 79.2% through a silicon membrane, and achieved flux of 327.36 ± 22.1 μg/cm2 through human skin after 24 h. So, nanoliposomes were proven as a suitable drug delivery system for topical delivery of VKO.
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8.
Dendrimers as efficient nanocarriers for the protection and delivery of bioactive phytochemicals.
Yousefi, M, Narmani, A, Jafari, SM
Advances in colloid and interface science. 2020;:102125
Abstract
The genesis of dendrimers can be considered as a revolution in nano-scaled bioactive delivery systems. These structures possess a unique potential in encapsulating/entrapping bioactive ingredients due to their tree-like nature. Therefore, they could swiftly obtain a valuable statue in nutraceutical, pharmaceutical and medical sciences. Phytochemicals, as a large proportion of bioactives, have been studied and used by scholars in several fields of pharmacology, medical, food, and cosmetic for many years. But, the solubility, stability, and bioavailability issues have always been recognized as limiting factors in their application. Therefore, the main aim of this study is representing the use of dendrimers as novel nanocarriers for phytochemical bioactive compounds to deal with these problems. Hence, after a brief review of phytochemical ingredients, the text is commenced with a detailed explanation of dendrimers, including definitions, types, generations, synthesizing methods, and safety issues; then is continued with demonstration of their applications in encapsulation of phytochemical bioactive compounds and their active/passive delivery by dendrimers. Dendrimers provide a vast and appropriate surface to entrap the targeted phytochemical bioactive ingredients. Several parameters can affect the yield of nanoencapsulation by dendrimers, including their generation, type of end groups, surface charge, core structure, pH, and ambient factors. Another important issue of dendrimers is related to their toxicity. Cationic dendrimers, particularly PAMAM can be toxic to body cells through attaching to the cell membranes and disturbing their functions. However, a number of solutions have been suggested to decrease their toxicity.
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9.
Nanocarriers as versatile delivery systems for effective management of acne.
Patel, R, Prabhu, P
International journal of pharmaceutics. 2020;:119140
Abstract
Acne vulgaris is a chronic inflammatory skin disorder affecting mostly females. It has a negative impact on the social life and psychological well-being of the individual. Its pathogenesis involves an exaggerated secretion of sebum, hyperkeratinisation of hair follicles, colonization of anaerobic microbes in the hair follicles, and inflammation. Conventional therapy for acne utilizes antibacterial and anti-inflammatory drugs. Systemic use of these drugs is associated with undesirable toxicities. Hence, topical delivery of anti-acne drugs is desired. However, topical delivery is hindered by poor aqueous solubility of drug and inadequate penetration across stratum corneum. Nanocarriers are endowed with immense potential to facilitate topical delivery of anti-acne drugs as monotherapy or in combination by a myriad of mechanisms including occlusive nature promoting skin hydration, providing sustained drug release thereby decreasing dosing frequency, follicular targeting, and protecting the labile active from degradation. Further, smart nanocarriers can deliver the anti-acne cargo in response to some stimulus present at the disease site precluding undesirable effects at non target sites. Nanocarriers have also been explored in photothermal and photodynamic therapy of acne for destruction of antibiotic resistant bacteria implicated in acne. This review focuses on the potential of a variety of nanocarriers for treatment of acne.
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10.
Development of an ultrasound triggered nanomedicine-microbubble complex for chemo-photodynamic-gene therapy.
Jang, Y, Kim, D, Lee, H, Jang, H, Park, S, Kim, GE, Lee, HJ, Kim, HJ, Kim, H
Nanomedicine : nanotechnology, biology, and medicine. 2020;:102194
Abstract
Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery.