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Human Pancreatic Polypeptide in a Phospholipid-Based Micellar Formulation

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An Erratum to this article was published on 27 March 2012

ABSTRACT

Purpose

Pancreatic polypeptide (PP) has important glucoregulatory functions and thereby holds significance in the treatment of diabetes and obesity. However, short plasma half-life and aggregation propensity of PP in aqueous solution, limits its therapeutic application. To address these issues, we prepared and characterized a formulation of PP in sterically stabilized micelles (SSM) that protects and stabilizes PP in its active conformation.

Methods

PP-SSM was prepared by incubating PP with SSM dispersion in buffer. Peptide-micelle association and freeze-drying efficacy of the formulation was characterized in phosphate buffers with or without sodium chloride using dynamic light scattering, fluorescence spectroscopy and circular dichroism. The degradation kinetics of PP-SSM in presence of proteolytic enzyme was determined using HPLC and bioactivity of the formulation was evaluated by in vitro cAMP inhibition study.

Results

PP self-associated with SSM and this interaction was influenced by presence/absence of sodium chloride in the buffer. The formulation was effectively lyophilized, demonstrating feasibility for its long-term storage. The stability of peptide against proteolytic degradation was significantly improved and PP in SSM retained its bioactivity in vitro.

Conclusions

Self-association of PP with phospholipid micelles addressed the delivery issues of the peptide. This nanomedicine should be further developed for the treatment of diabetes.

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Abbreviations

ANOVA:

analysis of variance

cAMP:

cyclic adenosine monophosphate

CD:

circular dichroism

CMC:

critical micellar concentration

CP:

chronic pancreatitis

DLS:

dynamic light scattering

DSPE-PEG2000 :

distearoyl phosphatidylethanolamine-polyethylene glycol2000

EMEM:

eagle’s minimum essential media

FD:

freeze-drying

IBMX:

3-Isobutyl-1-methylxanthine

NPY:

neuropeptide Y

NS:

normal saline

PB:

phosphate buffer

PBS:

phosphate buffered saline

PD:

pancreatogenic diabetes

PP:

pancreatic polypeptide

RP-HPLC:

peversed phase high pressure liquid chromatography

SD:

standard deviation

SSM:

sterically stabilized micelles

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ACKNOWLEDGMENTS & DISCLOSURES

The authors thank Dr. Bao-Shiang Lee for synthesizing PP used in the research.

The study was supported in part by NIH grant CA121797 and UIC university scholar award.

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Authors and Affiliations

  1. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Amrita Banerjee & Hayat Onyuksel

  2. Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Hayat Onyuksel

  3. Department of Biopharmaceutical Sciences (M/C 865) College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois, 60612-7231, USA

    Hayat Onyuksel

Authors
  1. Amrita Banerjee
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  2. Hayat Onyuksel
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Correspondence to Hayat Onyuksel.

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Banerjee, A., Onyuksel, H. Human Pancreatic Polypeptide in a Phospholipid-Based Micellar Formulation. Pharm Res 29, 1698–1711 (2012). https://doi.org/10.1007/s11095-012-0718-4

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  • DOI: https://doi.org/10.1007/s11095-012-0718-4

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