Molecular Mechanism of Poly(vinyl alcohol) Mediated Prevention of Aggregation and Stabilization of Insulin in Nanoparticles

Rawat, Sanjay; Gupta, Pawan; Kumar, Anil; Garg, Prabha; Suri, C. Raman; Sahoo, Debendra K.

doi:10.1021/mp5003653

Cited by 22 publications

(17 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The rational development of formulations derived from optimised interactions between proteins with specific excipients that effectively contribute to their stability and efficiency would be an important step-change in the field. Currently, there are attempts to use a combination of molecular docking and dynamics in selection of excipients to improve drug solubility [ 3 , 4 ] or to define the protein surfaces where the excipients may bind [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches

Barata

Zhang

Dalby

et al. 2016

IJMS

View full text Add to dashboard Cite

Protein formulation development relies on the selection of excipients that inhibit protein–protein interactions preventing aggregation. Empirical strategies involve screening many excipient and buffer combinations using force degradation studies. Such methods do not readily provide information on intermolecular interactions responsible for the protective effects of excipients. This study describes a molecular docking approach to screen and rank interactions allowing for the identification of protein–excipient hotspots to aid in the selection of excipients to be experimentally screened. Previously published work with Drosophila Su(dx) was used to develop and validate the computational methodology, which was then used to determine the formulation hotspots for Fab A33. Commonly used excipients were examined and compared to the regions in Fab A33 prone to protein–protein interactions that could lead to aggregation. This approach could provide information on a molecular level about the protective interactions of excipients in protein formulations to aid the more rational development of future formulations.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches

Barata

Zhang

Dalby

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…PVA has previously been explored as an excipient in a number of studies of bio-macromolecular stability. It has been found to be beneficial in some formulations of proteins, including insulin 37 , but benefit has not been seen consistently in other studies 38 39 40 . PVA may contribute to protein stability by hydrogen bonding of hydroxyl groups in PVA to the proteins.…”

Section: Discussionmentioning

confidence: 95%

Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation

Dulal

Walters

Hawkins

et al. 2020

Preprint

View full text Add to dashboard Cite

The global network of fridges and freezers known as the “cold chain” can account for a significant proportion of the total cost of vaccination and is susceptible to failure. Cost-efficient techniques to enhance stability of vaccines could prevent such losses and improve vaccination coverage, particularly in low income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving an excellent recovery of vaccines after storage at supraphysiological temperatures. This matrix is, however, prone to fragmentation and currently not suitable for clinical translation.Here, we report an investigation of alternative, potentially GMP compatible, fibrous matrices. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components. Our investigation shows that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to develop a custom-produced matrix with encouraging performance, as an initial step towards a biocompatible matrix for clinical translation. We discuss the path to transfer of the technology into clinical use, including potential obstacles.

show abstract

“…A common problem observed during purification of nanoparticles is clogging of filter pores. This is due to the presence of polyvinyl alcohol (PVA), a surfactant commonly used in the self-assembly of nanoparticles to improve their equilibrium in solution and reduce aggregation [ 30 ]. Thus, enhancing the self-assembly of TNPs in the reduction or total absence of PVA was a central task in this study.…”

Section: Discussionmentioning

confidence: 99%

Novel Chlorhexidine-Loaded Polymeric Nanoparticles for Root Canal Treatment

Quiram

Montagner

Palmer

et al. 2018

JFB

View full text Add to dashboard Cite

Persistence of microorganisms in dentinal tubules after root canal chemo-mechanical preparation has been well documented. The complex anatomy of the root canal and dentinal buffering ability make delivery of antimicrobial agents difficult. This work explores the use of a novel trilayered nanoparticle (TNP) drug delivery system that encapsulates chlorhexidine digluconate, which is aimed at improving the disinfection of the root canal system. Chlorhexidine digluconate was encapsulated inside polymeric self-assembled TNPs. These were self-assembled through water-in-oil emulsion from poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), a di-block copolymer, with one hydrophilic segment and another hydrophobic. The resulting TNPs were physicochemically characterized and their antimicrobial effectiveness was evaluated against Enterococcus faecalis using a broth inhibition method. The hydrophilic interior of the TNPs successfully entrapped chlorhexidine digluconate. The resulting TNPs had particle size ranging from 140–295 nm, with adequate encapsulation efficiency, and maintained inhibition of bacteria over 21 days. The delivery of antibacterial irrigants throughout the dentinal matrix by employing the TNP system described in this work may be an effective alternative to improve root canal disinfection.

show abstract

Molecular Mechanism of Poly(vinyl alcohol) Mediated Prevention of Aggregation and Stabilization of Insulin in Nanoparticles

Cited by 22 publications

References 57 publications

Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches

Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches

Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation

Novel Chlorhexidine-Loaded Polymeric Nanoparticles for Root Canal Treatment

Contact Info

Product

Resources

About