Formulation and process development of (recombinant human) deoxyribonuclease I as a powder for inhalation

Zijlstra, Gerrit; Ponsioen, Bart J; Hummel, Sylvia; Sanders, Niek N.; Hinrichs, Wouter L. J.; Boer, Anne H. de; Frijlink, Henderik W.

doi:10.1080/10837450802662820

Cited by 29 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The use of high temperatures during manufacturing of the implants may denature the antigen. However, in this study the implants were exposed to a temperature of 48 °C for a relatively short time (20 minutes), other studies showed that several proteins, such as DNAse [ 13 ], alkaline phosphatase [ 14 ], infliximab [ 15 ], hepatitis B surface antigen [ 11 ], and acyl-homoserine-lactone acylase [ 16 ] remained fully stable for several weeks at elevated temperatures (40–60 °C) when incorporated in inulin matrices. Hence, in this study the antigen was freeze-dried with inulin to stabilize the antigen.…”

Section: Resultsmentioning

confidence: 99%

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice

et al. 2018

Self Cite

View full text Add to dashboard Cite

A single-injection vaccine formulation that provides for both a prime and a boost immunization would have various advantages over a multiple-injection regime. For such a vaccine formulation, it is essential that the booster dose is released after a certain, preferably adjustable, lag time. In this study we investigated whether a core-shell based implant, containing ovalbumin as core material and poly(DL-lactic-co-glycolic acid) of various monomer ratios as shell material can be used to obtain such a booster release. An in vitro release study showed that the lag time after which the ovalbumin was released from the core-shell implant increased with increasing lactic to glycolic acid ratio of the polymer and ranged from 3–6 weeks. Fluorescence spectroscopy showed minimal differences between native ovalbumin and ovalbumin from core-shell implants that were incubated until just before the observed in vitro release. In addition, mice immunized with a subcutaneous inserted core-shell implant containing ovalbumin showed an ovalbumin-specific IgG1 antibody response after a lag time of 4 or 6–8 weeks. Moreover, delayed release of ovalbumin caused higher IgG1 antibody titers than conventional subcutaneous vaccination with ovalbumin dissolved in PBS. Collectively, these findings could contribute to the further development of a single-injection vaccine, making multiple injections of the vaccine superfluous.

show abstract

Section: Resultsmentioning

confidence: 99%

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…This being given, it is not surprising that 174 inulin was shown to be a good stabilizer of proteins under various conditions and stresses. Inulin has 175 been successfully used to stabilize proteins during spray-drying (Grasmeijer et (Zijlstra, Ponsioen, et al, 2009). The number of reducing groups is dependent on processing and 182 DP and is generally limited (Mensink et al, 2015).…”

Section: Protein Stabilization 157mentioning

confidence: 99%

“…As mentioned inulin has a small amount of reducing groups, meaning some protein degradation 252 because of the Maillard reaction might occur. Yet even under extreme storage conditions (85 °C / 0%RH 253 / 42days) this only played a minor role in protein stability of rhDNase, a protein that is sensitive to this 254 type of degradation(Zijlstra, Ponsioen, et al, 2009). In summary, inulin is a good stabilizer of proteins in 255 the dry state, and depending on the formulation and storage conditions it can be better than membranes and proteins, inulin has also been used to stabilize several pharmaceutically260 relevant systems.…”

mentioning

confidence: 98%

Inulin, a flexible oligosaccharide. II: Review of its pharmaceutical applications

Mensink

Frijlink

Maarschalk

et al. 2015

Carbohydrate Polymers

Self Cite

141

View full text Add to dashboard Cite

Inulin is a flexible oligosaccharide which has been used primarily in food for decades. Recently new applications in the pharmaceutical arena were described. In a previous review (Mensink et al. (2015). Carbohydrate Polymers, 130, 405) we described the physicochemical characteristics of inulin, characteristics which make inulin a highly versatile substance. Here, we review its pharmaceutical applications. Applications of inulin that are addressed are stabilization of proteins, modified drug delivery (dissolution rate enhancement and drug targeting), and lastly physiological and disease-modifying effects of inulin. Further uses of inulin include colon specific drug administration and stabilizing and adjuvating vaccine formulations. Overall, the uses of inulin in the pharmaceutical area are very diverse and research is still continuing, particularly with chemically modified inulins. It is therefore likely that even more applications will be found for this flexible oligosaccharide.

show abstract

“…However, the authors suggested that this drawback might be overcome by an improvement in the formulation design. In the present study, COLI-loaded particles for pulmonary inhalation were developed by using inulin (INU) as an excipient allowing particles with suitable aerodynamic properties to be formulated [25,26] and potentially reducing the irritating effects observed in humans with pure COLI sulfate. Additionally, INU was shown to be an excellent stabilizing agent for amorphous material due to its high glass transition temperature [27].…”

Section: Microparticle Formulation and Characterizationmentioning

confidence: 99%

Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery

et al. 2020

View full text Add to dashboard Cite

To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the solution. The amorphous COLI powder prepared by spray drying was characterized by a mass median aerodynamic diameter and fine particle fraction of 2.68 ± 0.07 µm and 59.5 ± 5.4%, respectively, when emitted from a Handihaler®. After intratracheal administration, the average pulmonary epithelial lining fluid (ELF): plasma area under the concentration versus time curves (AUC) ratios were 570 and 95 for the COLI solution and powder, respectively. However, the same COLI plasma concentration profiles were obtained with the two formulations. According to our pharmacokinetic model, this difference in ELF COLI concentration could be due to faster systemic absorption of COLI after the powder inhalation than for the solution. In addition, the COLI apparent permeability (Papp) across a Calu-3 epithelium model increased 10-fold when its concentration changed from 100 to 4000 mg/L. Based on this last result, we propose that the difference observed in vivo between the COLI solution and powder could be due to a high local ELF COLI concentration being obtained at the site where the dry particles impact the lung. This high local COLI concentration can lead to a local increase in COLI Papp, which is associated with a high concentration gradient and could produce a high local transfer of COLI across the epithelium and a consequent increase in the overall absorption rate of COLI.

show abstract

Formulation and process development of (recombinant human) deoxyribonuclease I as a powder for inhalation

Cited by 29 publications

References 45 publications

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice

Inulin, a flexible oligosaccharide. II: Review of its pharmaceutical applications

Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery

Contact Info

Product

Resources

About