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

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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.

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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

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Acknowledgments and Disclosures

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

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Authors and Affiliations

  1. Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, Pennsylvania, 15261, USA

    Peng Zhang, Yixian Huang, Xiang Gao & Song Li

  2. Department of Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA

    Alexander M. Makhov & Peijun Zhang

Authors
  1. Peng Zhang
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  2. Yixian Huang
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Correspondence to Song Li.

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Zhang, P., Huang, Y., Makhov, A.M. et al. Characterization of Spherulites as a Lipidic Carrier for Low and High Molecular Weight Agents. Pharm Res 30, 1525–1535 (2013). https://doi.org/10.1007/s11095-013-0990-y

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  • DOI: https://doi.org/10.1007/s11095-013-0990-y

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