Colonic Delivery of Vasoactive Intestinal Peptide Nanomedicine Alleviates Colitis and Shows Promise as An Oral Capsule

Abstract

Aim: To evaluate the efficacy of locally delivered nanomedicine, vasoactive intestinal peptide in sterically stabilized micelles (VIP-SSM) to the colon and conduct in vitro release studies of a potential oral formulation. Materials & methods: Intracolonic instillation of VIP-SSM was tested in a mouse model of dextran sulfate sodium-induced colitis. Based on the effective mouse dose, human equivalent dose containing nanomedicine powder was filled into enteric coated capsules for in vitro release testing. Results: Colonic delivery of VIP-SSM significantly alleviated colitis. VIP-SSM containing capsules completely dissolved at colonic pH allowing micelles to reform with active VIP. Capsule formulations exhibited reproducible release profiles when stored up to 6 weeks demonstrating stability. Conclusion: VIP-SSM is an effective nanomedicine formulation which appears to have potential for oral treatment of colitis in humans.

Keywords::

• colitis
• colonic delivery
• inflammatory bowel disease
• oral capsule form
• oral nanomedicine
• slc26a3
• sterically stabilized micelles
• targeted delivery
• VIP nanomedicine

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2020-0280

Author contributions

Initial conceptualization was performed by H Onyuksel and PK Dudeja. Evolution of conceptualization was performed by D Jayawardena. Investigations were performed by D Jayawardena, AN Anbazhagan, S Priyamvada and A Kumar. Resources were provided by PK Dudeja, H Onyuksel and S Saksena. Supervision was performed by PK Dudeja and H Onyuksel. D Jayawardena wrote the original draft. Review and editing were performed by all authors.

Financial & competing interests disclosure

These studies were supported by the NIDDK grants R01 DK54016, R01 DK92441 (PK Dudeja) and the Department of Veterans Affairs BX 002011 (PK Dudeja) and VA SRCS Award (IK6 BX005242, PK Dudeja), BX 002867 (S Saksena), BX004719 (A Kumar), UIC Dean’s Fellowship (D Jayawardena) and TUBITAK Award (H Onyuksel). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR15482 from the National Center for Research Resources, NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal studies performed were approved by the Animal Care Committee of the University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center (IL, USA). The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Acknowledgments

Special thanks to G Guzman, Pathologist at the University of Illinois at Chicago and staff at UIC RRC core imaging facility.

Additional information

Funding

These studies were supported by the NIDDK grants R01 DK54016, R01 DK92441 (PK Dudeja) and the Department of Veterans Affairs BX 002011 (PK Dudeja) and VA SRCS Award (IK6 BX005242, PK Dudeja), BX 002867 (S Saksena), BX004719 (A Kumar), UIC Dean’s Fellowship (D Jayawardena) and TUBITAK Award (H Onyuksel). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR15482 from the National Center for Research Resources, NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.