News

Maximizing the enzyme immobilization of enzymatic glucose biofuel cells through hierarchically structured reduced graphene oxide

Maximizing the enzyme immobilization of enzymatic glucose biofuel cells through hierarchically structured reduced graphene oxide

Joonyoung Lee, Kyuhwan Hyun, Jae Min Park, Ho Seok Park, Yongchai Kwon

Summary

The number of immobilized glucose oxidase (GOx) molecules is considerably increased by the structural modification of reduced graphene oxide (rGO), and the performance of enzymatic biofuel cells (EBFCs) is positively affected by the modification process. To do this, new rGO with three-dimensional open porous structure is formed by spray freeze drying method (sprGO), while tetrathiafulvalene (TTF) as mediator, and GOx are sequentially immobilized onto sprGO. To improve the loading amount of catalyst, rGO structure is modified to open porous sprGO structure possessing numerous anchoring sites, after which gelatin film crosslinked by glutaraldehyde is fabricated onto sprGO to prevent any losses of other components (sprGO/[TTF-GOx]/crosslinked-gelatin). Specific surface area and charge transfer resistance of sprGO are quantitatively measured, and the actual amount of immobilized GOx and the performance of EBFC using this catalyst are electrochemically examined. With this, it is found that the amount of GOx immobilized in sprGO/[TTF-GOx]/crosslinked-gelatin is twice better that in rGO/[TTF-GOx]/crosslinked-gelatin. More specifically, EBFC using this catalyst shows open circuit voltage of 0.85 V and maximum power density of 380 μW/cm2, and this is 1.4 times better than that using rGO/[TTF-GOx]/crosslinked-gelatin. These results indicate that the amount of immobilized GOx strongly affects the performance capabilities of EBFCs.

Keywords

biofuel cell, freeze-drying method, glucose oxidase, open porous structure, spray frozen reduced graphene oxide

Improvement of Drug Delivery Properties of Risperidone via Preparation of Oral Disintegration Tablet Containing Nanostructured Microparticles

Improvement of Drug Delivery Properties of Risperidone via Preparation of Oral Disintegration Tablet Containing Nanostructured Microparticles

Motahare salarvanda, Zeinab Aref Darabi, Vahid Ramezani

Abstract

Introduction: The aim of this study was to improve the dissolution profile of risperidone and increase the compliance of psychotic patients through the design of an oral disintegration tablet­ (ODT) of microparticles containing nanoparticles.

Methods and Results: In order to prepare nanoparticles, the effect of six surfactants on the size and stability of nanoparticles was evaluated. The nanoaggregate fabricated via the spray freeze drying ­(SFD) process using mannitol, lactose and maltodextrin as a matrix agent. Nine formulations were prepared and evaluated on the particle size, dissolution rate , and other physicochemical properties.Finally, the formulations of ODT were designed and evaluated.

The results show that using of cremophore EL and hydroxypropyl methyl cellulose E15 with the synergic effect can develop the risperidone nanosuspension with nano range particle size (~188 nm). Also, it is showed that fabrication of risperidone microparticles containig nanoparticles enhanced the drug dissolution up to 2 min for lactose-based microparticles (as a superior formulation) that is very faster time than coarse risperidone powder with dissolution time of 60 min. the formulations of ODT containing 10% Sodium Starch Glycolate and 88% Microcrystalline Cellulose as Super disintegrants were selected with a disintegration time of fewer than 30 seconds and dissolution time of 10 min in superior formulation.

Conclusions: It is indicated that the simultaneous use of non-ionic surfactants can prepare risperidone nanoparticles by creating a steric barrier around the drug particles. In addition, the dissolution rate of risperidone has increased significantly due to the small particle size of nanoparticles according to Noyes-Whitney equation. The use of sugars maintains the size of the nanoparticles and prevents the formation of irreversible coalescence of nanoparticles. Thus, this investigation shows that the preparation of microparticles containing nanoparticles using SFD is an easy and usable method for improving the dissolution profile of many low solubility drugs.

Keywords

nanoparticles, dissolution, risperidone, oral disintegration tab

Post-Processing Techniques for the Improvement of Liposome Stability

Post-Processing Techniques for the Improvement of Liposome Stability

Ji Young Yu, Piyanan Chuesiang, Gye Hwa Shin, Hyun Jin Park

Abstract

Liposomes have been utilized as a drug delivery system to increase the bioavailability of drugs and to control the rate of drug release at the target site of action. However, the occurrence of self-aggregation, coalescence, flocculation and the precipitation of aqueous liposomes during formulation or storage can cause degradation of the vesicle structure, leading to the decomposition of liposomes. To increase the stability of liposomes, post-processing techniques have been applied as an additional process to liposomes after formulation to remove water and generate dry liposome particles with a higher stability and greater accessibility for drug administration in comparison with aqueous liposomes. This review covers the effect of these techniques including freeze drying, spray drying and spray freeze drying on the stability, physicochemical properties and drug encapsulation efficiency of dry liposomes. The parameters affecting the properties of liposomes during the drying process are also highlighted in this review. In addition, the impact of using a protective agent to overcome such limitations of each process is thoroughly discussed through various studies.

Keywords

post-processing techniques; liposome stability; freeze drying; spray drying; spray freeze drying

Influence of the PuO2 content on the sintering behaviour of UO2-PuO2 freeze-granulated powders under reducing conditions

Influence of the PuO2 content on the sintering behaviour of UO2-PuO2 freeze-granulated powders under reducing conditions

Julie Simeon, Florent Lebreton, Laure Ramond, Nicolas Clavier, Guillaume Bernard-Granger

Abstract

The sintering behaviour of freeze-granulated UO2-PuO2 powders containing 33 and 15 mol% Pu/(U + Pu) was investigated under reducing conditions up to 1700 °C. For both compositions, the “grain size versus relative density” trajectory was constructed. All the experimental points form a single trajectory meaning that a relative density/grain size pair obtained after sintering seems independent of the thermal path (heating rate, soak time, soak temperature) and of the Pu content. Exploiting the “grain size versus relative density trajectory” enabled also to propose that densification was controlled by grain boundary diffusion and grain growth by the grain boundaries whatever the Pu content. An activation energy around 510 kJ/mol was obtained for densification, which was close to the value reported for the grain boundary diffusion of plutonium cations in U1-xPuxO2 polycrystals. Whatever the Pu/(U + Pu) content, the sintered microstructure of 98 % dense samples possesses a homogeneous distribution of plutonium and uranium cations.

Keywords

Sintering, Ceramics, Oxides, Microstructure, MOX

Mixed bacteriophage ms2-l2 vlps elicit long-lasting protective antibodies against hpv pseudovirus 51

Mixed bacteriophage ms2-l2 vlps elicit long-lasting protective antibodies against hpv pseudovirus 51

Abstract

Three prophylactic vaccines are approved to protect against HPV infections. These vaccines are highly immunogenic. The most recent HPV vaccine, Gardasil-9, protects against HPV types associated with ~90% of cervical cancer (worldwide). Thus, ~10% of HPV-associated cancers are not protected by Gardasil-9. Although this is not a large percentage overall, the HPV types associated with 10% of cervical cancer not protected by the current vaccine are significantly important, especially in HIV/AIDS patients who are infected with multiple HPV types. To broaden the spectrum of protection against HPV infections, we developed mixed MS2-L2 VLPs (MS2-31L2/16L2 VLPs and MS2-consL2 (69-86) VLPs) in a previous study. Immunization with the VLPs neutralized/protected mice against infection with eleven high-risk HPV types associated with ~95% of cervical cancer and against one low-risk HPV type associated with ~36% of genital warts & up to 32% of recurrent respiratory papillomatosis. Here, we report that the mixed MS2-L2 VLPs can protect mice from three additional HPV types: HPV51, which is associated with ~0.8% of cervical cancer; HPV6, which is associated with up to 60% of genital warts; HPV5, which is associated with skin cancers in patients with epidermodysplasia verruciformis (EV). Overall, mixed MS2-L2 VLPs can protect against twelve HPV types associated with ~95.8% of cervical cancers and against two HPV types associated with ~90% of genital warts and >90% recurrent respiratory papillomatosis. Additionally, the VLPs protect against one of two HPV types associated with ~90% of HPV-associated skin cancers in patients with EV. More importantly, we observed that mixed MS2-L2 VLPs elicit protective antibodies that last over 9 months. Furthermore, a spray-freeze-dried formulation of the VLPs is stable, immunogenic, and protective at room temperature and 37 °C.

Keywords

human papillomaviruses; thermostable vaccines; protection; MS2 bacteriophage; virus-like particles; spray-freeze-drying; longevity

Spray freeze dried lyospheres® for nasal administration of insulin

Spray freeze dried lyospheres® for nasal administration of insulin

Tuğrul Mert Serim, Jan Kožák, Annika Rautenberg, Ayşe Nurten Özdemir, Yann Pellequer, Alf Lamprecht

Abstract

Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters ranged from 190 to 250 µm, depending on the excipient composition. Based on the low density, lyospheres resulted in a nasal deposition rates of 90% or higher. When tested in vivo for their glycemic potential in rats, an insulin-taurocholate combination revealed a nasal bioavailability of insulin of 7.0 ± 2.8%. A complementary study with fluorescently labeled-dextrans of various molecular weights confirmed these observations, leading to nasal absorption ranging from 0.7 ± 0.3% (70 kDa) to 10.0 ± 3.1% (4 kDa). The low density facilitated nasal administration in general, while the high porosity ensured immediate dissolution of the particles. Additionally, due to their stability, lyospheres provide an extremely promising platform for nasal peptide delivery.

Keywords

spray freeze drying, lyophilization, nasal drug delivery, peptide formulations, porous particles, pharmacokinetic

Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice.

Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice.

Changjiao Gan, Wenbo Luo, Yunzhou Yu, Zhouguang Jiao, Sha Li, Duo Su, Junxia Feng, Xiaodong Zhao, Yefeng Qiu, Lingfei Hu, Dongsheng Zhou, Xiaolu Xiong, Jinglin Wang & Huiying Yang

Abstract

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

Inhaled Dry Powder Formulation of Tamibarotene, a Broad-Spectrum Antiviral against Respiratory Viruses Including SARS-CoV-2 and Influenza Virus

Inhaled Dry Powder Formulation of Tamibarotene, a Broad-Spectrum Antiviral against Respiratory Viruses Including SARS-CoV-2 and Influenza Virus

Qiuying Liao, Shuofeng Yuan, Jianli Cao, Kaiming Tang, Yingshan Qiu, Han Cong Seow, Rico Chi-Hang Man, Zitong Shao, Yaoqiang Huang, Ronghui Liang, Jasper Fuk-Woo Chan, Kwok-Yung Yuen, Jenny Ka-Wing Lam

Abstract

In response to the epidemic and pandemic threats caused by emerging respiratory viral infections, a safe and efficient broad-spectrum antiviral therapy at early onset of infection can significantly improve patients’ outcome. Inhaled dry powder is easy to administer and delivers antiviral agent directly to the primary site of infection, thereby minimizing systemic side effects. Here, spray freeze drying (SFD) technique is employed to formulate tamibarotene, a retinoid derivative with broad-spectrum antiviral activity, as inhalable powder. The SFD tamibarotene powder exhibits desirable physicochemical and aerodynamic properties for inhalation. Pulmonary delivery of tamibarotene powder results in rapid absorption and higher bioavailability compared with intraperitoneal injection of unformulated drug in animals. More importantly, inhalation or intranasal delivery of SFD tamibarotene formulation displays broad-spectrum antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus, and pandemic 2009 influenza A virus (H1N1) in mouse and hamster models by targeting lower or upper airways, and the efficacy is comparable or superior to the commercially available antivirals remdesivir and zanamivir against specific virus. These results present a promising strategy to combat various respiratory viral infections including SARS-CoV-2 and influenza virus, or even co-infection.

Keywords

broad-spectrum antiviral drugs, drug repurposing, influenza, pulmonary delivery, severe acute respiratory syndrome coronavirus 2

Comparative Study on Compaction and Sintering Behavior of Spray and Freeze Granulated Magnesium Aluminate Spinel Powder

Comparative Study on Compaction and Sintering Behavior of Spray and Freeze Granulated Magnesium Aluminate Spinel Powder

Swathi Manivannan, Papiya Biswas, Prasenjit Barick, Sweety Kumari, Bhaskar Prasad Saha & Roy Johnson

Abstract

Commercially procured magnesium aluminate (MgAl2O4) spinel powder with average particle size of 300 nm and irregular morphology were spray and freeze granulated. The granules were characterized for the texture, strength, granule size and its distribution. In order to evaluate the flowability of granules, rheological parameters, such as Carr index and Hausner ratio were measured. The granules were further subjected to quasi-static compaction under loading, unloading conditions and compaction curves were constructed. Compaction coefficients thus obtained were correlated with granulation conditions and other parameters including green densities. Compacted green samples were also subjected to flexural strength measurements following ASTM standards and fractographs were observed under FESEM. A Carr index of 13.7 and Hausner ratio of 1.16 were obtained for freeze dried granules indicating the superiority in flow behavior as compared to its spray granulated counterpart, thereby showing a better compaction behavior: compaction coefficient of 5.9 in combination with higher true and predicted green density values and lower granule strength of 1.22 MPa. The green samples exhibited a flexural strength of 11 and 12.5 MPa and compressive strength of 2.44 and 1.22 MPa for spray and freeze granulated sample, respectively. The above observations were also complemented by the fractographs.

Keywords

Spray granulation, Freeze granulation, Spinel, Compaction curve

Morphology of alumina granules obtained by spray freeze drying with twin-fluid atomization

Morphology of alumina granules obtained by spray freeze drying with twin-fluid atomization

Ruslan Kuzmin, Sergey Veselov, Nina Cherkasova, Vladimir Bataev

Abstract

This study presents the results of the morphological dependence of alumina granules obtained by spray freeze drying (SFD) with twin-fluid atomization. It is shown that the introduction of 1-, 2- and 4-wt.% polyvinyl alcohol (PVA) as a binder in an alumina suspension leads to the formation of irregular granules. Depending on atomization conditions, spherical, “tadpole-like,” granule-satellite and granule aggregates may form during SFD. Increasing the flight time of droplets before the fixing of their shape when they come in contact with liquid nitrogen effectively contributes to the spheroidization of alumina granules. Compacting PVA-free SFD granules leads to the formation of diagonal flaws in a green-body structure. Adding PVA prevents the abovementioned defects by increasing the strength of alumina granules. Increasing the amount of PVA leads to an increase in “tadpole-like” granule content and, consequently, a decrease in a green-body density.