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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.

Combination of copigmentation and encapsulation strategies for the synergistic stabilization of anthocyanins

Combination of copigmentation and encapsulation strategies for the synergistic stabilization of anthocyanins

Chen Tan, Younas Dadmohammadi, Michelle C. Lee, Alireza Abbaspourrad

Abstract

Copigmentation and encapsulation are the two most commonly used techniques for anthocyanin stabilization. However, each of these techniques by itself suffers from many challenges associated with the simultaneous achievement of color intensification and high stability of anthocyanins. Integrating copigmentation and encapsulation may overcome the limitation of usage of a single technique. This review summarizes the most recent studies and their challenges aiming at combining copigmentation and encapsulation techniques. The effective approaches for encapsulating copigmented anthocyanins are described, including spray/freeze-drying, emulsification, gelation, polyelectrolyte complexation, and their combinations. Other emerging approaches, such as layer-by-layer deposition and ultrasonication, are also reviewed. The physicochemical principles underlying the combined strategies for the fabrication of various delivery systems are discussed. Particular emphasis is directed toward the synergistic effects of copigmentation and encapsulation, for example, modulating roles of copigments in the processes of gelation and complexation. Finally, some of the major challenges and opportunities for future studies are highlighted. The trend of integrating copigmentation and encapsulation has been just started to develop. The information in this review should facilitate the exploration of the combination of multistrategy and the fabrication of robust delivery systems for copigmented anthocyanins.

Effect of drying techniques on yield, nutritional, minerals of wild banana pulp (Musa balbisiana Colla): physicochemical and morphological characterization thereof

Effect of drying techniques on yield, nutritional, minerals of wild banana pulp (Musa balbisiana Colla): physicochemical and morphological characterization thereof

Twinkle Borah, Nooreen Washmin, Nayan Jyoti Bora, Jadumoni Saikia, Padma Sangmu Bomzon, Tobiul Hussain Ahmed, Prasenjit Manna, Siddhartha Proteem Saikia, Dipanwita Banik

Abstract

Purpose

The study was aimed to compare the effect of three drying techniques viz., spray, freeze and hot air oven (HAO) drying on yield, nutritional parameters, minerals and physicochemical and morphological characterization of wild banana pulp (Musa balbisiana Colla).

Design/methodology/approach

Contents of carbohydrate was estimated by Anthrone reagent, protein by Kjeldahl, fat by Soxhlet, dietary fiber and ash by Association of Official Analytical Chemists (AOAC), minerals by Atomic Absorption Spectrophotometry, gross calorific value by Bomb calorimeter, moisture by moisture analyzer, water activity by water activity meter, morphological characterization by Scanning Electron Microscopy (SEM), statistical level of significance at p < 0.05 by ANOVA, predictive modeling by simple and multiple linear regression.

Findings

Freeze and HAO drying were standardized with matured (stage 2) and spray drying with ripe bananas (stage 6). Freeze drying showed highest yield (76.69 ± 0.15%), minerals viz., K (1175.67 ± 1.41), Fe (2.27 ± 0.09), Mg (120.33 ± 0.47), Mn (4.40 ± 0.28) mg/100 g, protein (7.53 ± 0.14%), lesser moisture (7.95 ± 0.01%), water activity (0.17 ± 0.02aw), hygroscopicity (6.37 ± 1.09%), well dispersed particles by SEM. HAO drying exhibited highest dietary fiber (18.95 ± 0.24%), gross calorific value 357.17 kcal/100 gm, higher solubility (47.22 ± 0.86%). Spray drying showed highest carbohydrate (85.29 ± 0.01%), lowest yield (28.26 ± 0.32%), required 30.5% adjuncts.

Research limitations/implications

Effect of three drying techniques and use of adjuncts were not uniform for ripe and matured bananas.

Practical implications

Commercial utilization of seeded wild banana.

Social implications

Value addition of wild banana in Assam, India

Originality/value

Freeze drying of mature wild banana pulp (M. balbisiana) was found as best technique utilizing lesser energy.

Keywords

Musa balbisiana, Wild banana, Pulp, Powder, Spray, Oven, Freeze drying, Nutritional, Physicochemical

Thermolysis and Sensitivities of Nanometer Ammonium Nitrate Prepared by Ultra-low Temperature Spray Freeze Drying Method

Thermolysis and Sensitivities of Nanometer Ammonium Nitrate Prepared by Ultra-low Temperature Spray Freeze Drying Method

Yi Wang, Xiaolan Song, Fengsheng Li

Abstract

Nanometer (nano) ammonium perchlorate (AP) and ammonium nitrate (AN) were prepared with 2D network structures by the ultra-low temperature spray method. Scanning electron microscopy (SEM), X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis/infrared spectrometry (TG-IR) were employed to probe the micron structure, crystal phase, and thermal decomposition of nano AP and nano AN. SEM images revealed that the sizes of nano AP and AN were in the nanometer scale (<100 nm) in one dimension. XRD patterns showed that the crystal phases of nano AP and AN were in accordance with those of raw AP and raw AN, respectively. DSC traces indicated that the thermal decomposition process of AP depended on its particle size, while the thermolysis of AN was independent of the particle size of AN. TG-IR analyses illustrated that the decomposition products of nano AP were NO2, N2O, HCl and H2O, with a small amount of NOCl, and the main decomposition products of nano AN were N2O and H2O, with a small amount of NH3. The results of mechanical sensitivity tests indicated that nano AP was more sensitive than raw AP and both nano AN and raw AN were very insensitive to impact and friction stimuli.

Keywords

nano AP; nano AN; liquid nitrogen; freeze drying; thermolysis

Effects of Non-covalent Functionalization and Initial Mixing Methods on SWNT/PP and SWNT/EVOH Composites

Effects of Non-covalent Functionalization and Initial Mixing Methods on SWNT/PP and SWNT/EVOH Composites

Mahesh Parit, Virginia A. Davis

Abstract

We report that a simple, low-cost type of spray-freeze drying (SFD) significantly improves the dispersion of single-walled carbon nanotubes (SWNTs) in thermoplastic polymers. Conventional SFD requires costly specialized equipment and large amounts of material, both of which are impediments to laboratory research on nanomaterial composites. Our method uses more readily available equipment and can be adapted to use milligrams to grams of material. A household spray bottle containing an aqueous nanomaterial dispersion is used to spray the dispersion into a dish of liquid nitrogen. The resulting material is then lyophilized in a standard laboratory freeze dryer. The usefulness of this simplified method was explored by comparing the properties of polypropylene (PP) composites produced by this method to those produced by a previously reported rotary evaporation method in which the dispersion is vacuum-dried onto the polymer. The role of the initial dispersion state was explored by using pristine SWNTs as well as SWNTs stabilized by two common SWNT stabilizers: polyvinylpyrrolidone (PVP) and sodium dodecyl sulfate. Based on rheological, thermal, and morphological characterization, the porous friable structures produced by SFD resulted in better SWNT dispersion compared to composites produced by a previously reported rotary evaporation method. However, the PP/PVP-SWNT nanocomposites produced by both methods contained large aggregates. To verify that this aggregation behavior was the result of thermodynamic incompatibility between PP and PVP, ethylene vinyl alcohol (EVOH) nanocomposites containing PVP-SWNT were also produced using the SFD method. The results of this research show how a low-cost alternative to SFD along with careful consideration of compatibility is a promising approach to produce nanocomposites.

Keywords

Functionalization, Colloids, Nanocomposites, Carbon nanotubes, Polymers