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Pharmaceutical Research

, Volume 30, Issue 6, pp 1525–1535 | Cite as

Characterization of Spherulites as a Lipidic Carrier for Low and High Molecular Weight Agents

  • Peng Zhang
  • Yixian Huang
  • Alexander M. Makhov
  • Xiang Gao
  • Peijun Zhang
  • Song Li
Research Paper

Abstract

Purpose

To develop spherulite formulations to achieve high entrapment efficiency for both small and macromolecules as well as cell-type specific delivery.

Methods

Spherulites of various compositions were prepared, and lipid-PEG was incorporated through post-insertion. Calcein and FITC-labeled albumin were employed as model drugs for small and macromolecules. The spherulites were characterized with respect to entrapment efficiency, size, structure, and release kinetics, and the morphology was examined via cryo-EM. Finally, SV119-decorated spherulites were examined for their selective uptake by cancer cells.

Results

The spherulites are 170 ~ 290 nm in size. A loading efficiency of 55 ~ 60% can be consistently achieved for both calcein and albumin under optimized conditions. Cryo-EM shows the onion-like morphology consistent with the structure of multilamellar liposomes. A t1/2 of 39.3 h and 69.7 h in cargo release in serum was observed before and after PEG decoration, and incorporation of SV119 led to selective delivery of rhodamine-labeled spherulites to PC-3 tumor cells.

Conclusions

Our optimized formulations may represent a platform with simple preparation approach, relatively small particle size, high drug loading efficiency for both low and high molecular weight agents, and slow release kinetics for selective delivery of various types of therapeutics to target cells.

KEY WORDS

cryo-electron microscopy entrapment efficiency multilamellar liposomes spherulites targeted drug delivery 

Abbreviations

BS10

brij S10

BSA

bovine serum albumin

CH

cholesterol

Cryo-EM

cryo-electron microscopy

Dex

dexamethasone

DLS

dynamic light scattering

DMEM

Dulbecco’s modified eagle’s medium

DPBS

Dulbecco’s phosphate buffered saline

DSPE-PEG2k

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]

EE

entrapment efficiency

EPR

enhanced permeability and retention

FBS

fetal bovine serum

FITC

fluorescein isothiocyanate

FITC-BSA-SU

fluorescein isothiocyanate-labeled succinylated bovine serum album

MeO-PEG5k

methoxypoly(ethylene glycol)-5000

MLV

multilamellar vesicles

SPC

soybean L-α-phosphatidylcholine

TW80

polyoxyethylene 80 sorbitan monooleate

Notes

Acknowledgments and Disclosures

This work was supported in part by NIH grants R01HL091828, R21CA128415 and R21CA155983.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Peng Zhang
    • 1
  • Yixian Huang
    • 1
  • Alexander M. Makhov
    • 2
  • Xiang Gao
    • 1
  • Peijun Zhang
    • 2
  • Song Li
    • 1
  1. 1.Center for Pharmacogenetics, Department of Pharmaceutical SciencesSchool of Pharmacy, University of PittsburghPittsburghUSA
  2. 2.Department of Structural Biology, School of MedicineUniversity of PittsburghPittsburghUSA

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