Future of Sustained Protein Delivery

Vaishya, Ravi; Mitra, Ashim K.

doi:10.4155/tde.14.86

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…The controlled release of protein into the cytosol over time is a largely unmet need that would provide for a high level of control over protein activity within the cell. 23 Recent work by Wojnilowicz et al demonstrated endosomal lysis and subsequent burst release of highly branched and rigid cationic polymers, such as dendritic glycogen, 24 while Rehman et al demonstrated burst release, but not complete endosomal rupture, with flexible linear PEI (LPEI) and passive "leaky" release with liposomes where a distinct burst event could not be identified. 22 Whether carrier architecture favors burst versus sustained release and over what time frame is crucial information that will allow protein carriers to be engineered to optimize therapeutic parameters.…”

Section: ■ Introductionmentioning

confidence: 99%

Regulation of Proteins to the Cytosol Using Delivery Systems with Engineered Polymer Architecture

et al. 2021

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Intracellular protein delivery enables selective regulation of cellular metabolism, signaling, and development through introduction of defined protein quantities into the cell. Most applications require that the delivered protein has access to the cytosol, either for protein activity or as a gateway to other organelles such as the nucleus. The vast majority of delivery vehicles employ an endosomal pathway however, and efficient release of entrapped protein cargo from the endosome remains a challenge. Recent research has made significant advances toward efficient cytosolic delivery of proteins using polymers, but the influence of polymer architecture on protein delivery is yet to be investigated. Here, we developed a family of dendronized polymers that enable systematic alterations of charge density and structure. We demonstrate that while modulation of surface functionality has a significant effect on overall delivery efficiency, the endosomal release rate can be highly regulated by manipulating polymer architecture. Notably, we show that large, multivalent structures cause slower sustained release, while rigid spherical structures result in rapid burst release.

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Section: ■ Introductionmentioning

confidence: 99%

Regulation of Proteins to the Cytosol Using Delivery Systems with Engineered Polymer Architecture

et al. 2021

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“…There has been a substantial rise in the number of protein and peptide biologics in clinical trials for various diseases (Vaishya et al, 2014; Vaishya and Mitra, 2014). Recent advancements in protein engineering allow for rapid development of new peptide/protein therapeutics along with improved understanding of pharmacokinetics and pharmacodynamics.…”

Section: Introductionmentioning

confidence: 99%

“…MPs are formulated with PLGA-glucose polymer for delivery over a period of 4 weeks. Lactide- and glycolide-based biodegradable polymers such as poly(D,L-lactide-coglycolide) (PLGA) and poly(D,L-lactide) (PLA) are FDA-approved and have been widely investigated for the sustained release of therapeutic peptides and proteins (Vaishya et al, 2014; Vaishya and Mitra, 2014). However, these polymers may not be suitable for delivering peptide and protein biologics as recent studies indicate that peptides/proteins are susceptible to acylation within the microenvironment of particles during release (Ghassemi et al, 2012; Ibrahim et al, 2005; Murty et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles

Vaishya

Mandal

Gokulgandhi

et al. 2015

International Journal of Pharmaceutics

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Acylation of peptide has been reported for a number of peptides and proteins during release from polymers comprising of lactide and glycolide. We hypothesize that reversible hydrophobic ion-pairing (HIP) complex may minimize octreotide acylation during release. Sodium dodecyl sulfate (SDS), dextran sulfate A (DSA, Mw 9–20kDa) and dextran sulfate B (DSB, Mw 36–50kDa) were selected as ion-pairing agents to prepare reversible HIP complex with octreotide. Complexation efficiency was optimized with respect to the mole ratio of ion-pairing agent to octreotide to achieve 100% complexation of octreotide. Dissociation studies suggested that DSA-octreotide and DSB-octreotide complexes dissociate completely at physiological pH in presence of counter ions unlike SDS-octreotide complex. DSA-octreotide and DSB-octreotide complex encapsulated PLGA microparticles (DSAMPs and DSBMPs) were prepared using the S/O/W emulsion method. Entrapment efficiencies for DSAMPs and DSBMPs were 74.7±8.4% and 81.7±6.3%, respectively. In vitro release of octreotide was performed by suspending MPs in gel. A large fraction of peptide was released in chemically intact form and <7% was acylated from DSAMPs and DSBMPs in gel over 55 days. Therefore, HIP complexation could be a viable strategy to minimize acylation of peptides and proteins during extended release from lactide and glycolide based polymers.

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The ocular pharmacokinetics and biodistribution of phospho-sulindac (OXT-328) formulated in nanoparticles: Enhanced and targeted tissue drug delivery

Wen

Muratomi

Huang

et al. 2019

International Journal of Pharmaceutics

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Future of Sustained Protein Delivery

Abstract: “Despite limitations associated with every approach, delivery of proteins for an extended duration in a controlled manner is achievable… a clinically acceptable formulation that delivers proteins over a period of months is largely an unmet need.”

Cited by 6 publications

References 18 publications

Regulation of Proteins to the Cytosol Using Delivery Systems with Engineered Polymer Architecture

Regulation of Proteins to the Cytosol Using Delivery Systems with Engineered Polymer Architecture

Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles

The ocular pharmacokinetics and biodistribution of phospho-sulindac (OXT-328) formulated in nanoparticles: Enhanced and targeted tissue drug delivery

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