AAPS PharmSciTech

, 20:66 | Cite as

Multi-Layered Nanomicelles as Self-Assembled Nanocarrier Systems for Ocular Peptide Delivery

  • Abhirup Mandal
  • Pratikkumar Patel
  • Dhananjay Pal
  • Ashim K. MitraEmail author
Research Article


Despite the great potential of peptides as therapeutics, there is an unmet challenge in sustaining delivery of sufficient amounts in their native forms. This manuscript describes a novel nanocarrier capable of delivering functional small peptides in its native form. Self-assembling multi-layered nanomicelles composed of two polymers, polyoxyethylene hydrogenated castor oil 40 (HCO-40) and octoxynol 40 (OC-40), were designed to combine hydrophilic interaction and solvent-induced encapsulation of peptides and proteins. The polymers are employed to encapsulate peptide or protein in the core of the organo-nanomicelles which are further encapsulated with another layer of the same polymers to form an aqueous stable nanomicellar solution. The size of the multi-layered nanomicelles ranges from ~ 16 to 20 nm with zeta potential close to neutral (~ − 2.44 to 0.39 mV). In vitro release studies revealed that octreotide-loaded multi-layered nanomicelles released octreotide at much slower rate in simulated tear fluid (STF) (~ 27 days) compared to PBST (~ 11 days) in its native form. MTT assay demonstrated negligible toxicity of the multi-layered nanomicelles at lower concentrations in human retinal pigment epithelial (HRPE, D407), human conjunctival epithelial (CCL 20.2), and rhesus choroid-retinal endothelial (RF/6A) cells. This work demonstrates an efficient small peptide delivery platform with significant advantages over existing approaches, as it does not require modification of the peptide, is biodegradable, and has a small size and high loading capacity.


micelles sustained release self-assembly formulation acylation octreotide mass spectrometry 



This work was supported by R01EY09171-16 and R01EY010659-14 grants from the National Institute of Health.

Compliance with Ethical Standards

Conflict of Interest

This invention has been disclosed to the University of Missouri-Kansas City for potential patent filing.

Supplementary material

12249_2018_1267_MOESM1_ESM.docx (376 kb)
ESM 1 (DOCX 376 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Abhirup Mandal
    • 1
  • Pratikkumar Patel
    • 1
  • Dhananjay Pal
    • 1
  • Ashim K. Mitra
    • 1
    • 2
    Email author
  1. 1.Division of Pharmacology and Pharmaceutical Sciences, School of PharmacyUniversity of Missouri-Kansas CityKansas CityUSA
  2. 2.Vision Research Center, Department of Ophthalmology, School of MedicineUniversity of Missouri-Kansas CityKansas CityUSA

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