Skip to main content

Advertisement

SpringerLink
Log in

Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature Hollow Microneedle for Treatment of Intermittent Fecal Incontinence

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

A low temperature hollow microneedle system was devised to deliver sol-gel transition formulation near the surface of the skin for extended release and local delivery of drug by a non-invasive method. This new system can improve treatment of intermittent fecal incontinence.

Method

The low-temperature system was integrated with a hollow microneedle to maintain the low temperature of the sol formulation. Various sol-gel formulations using Pluronic F-127 (PF-127) and Hydroxy-propyl-methyl-cellulose (HPMC) were prepared, and their gelation temperature, flow property, and diffusion retardation were observed. Resting anal sphincter pressure in response to a phenylephrine (PE) sol-gel formulation was measured using an air-charged catheter. The biocompatibility of the sol-gel PE formulation was evaluated by observing the immunological response.

Results

When the PF-127 25%, HPMC 1% and PE formulation (PF25-HPMC1-PE) was injected through the peri-anal skin of the rat in vivo, the highest pressure on the anal sphincter muscle occurred at 6–8 h and anal pressure increased and lasted twice as long as with the phosphate-buffered saline (PBS)-PE formulation. There was no significant difference in the number of mast cells after administration into the rat in vivo between the PF25-HPMC1-PE formulation and the PBS-PE formulation.

Conclusion

The combination of a low-pain hollow microneedle system and an injectable sol-gel formulation improved the efficacy of treatment of intermittent fecal incontinence. A low-temperature hollow microneedle system using a sol-gel formulation has many applications in medical treatments that require depot effect, local targeting, and pain control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

HPMC :

Hydroxy-propyl-methyl-cellulose

PBS :

Phosphate-buffered saline

PBS-PE :

Phosphate-buffered saline and PE formulation

PE :

Phenylephrine

PF-127 :

Pluronic F-127

PF-15 :

Pluronic 15% (w/w))

PF-25 :

Pluronic 25% (w/w)),

PF-15/HPMC-1 :

Pluronic 15% (w/w) and hydroxyl propyl methyl cellulose (HPMC) 1% (w/w)

PF-25/HPMC-1 :

Pluronic 25% (w/w) and hydroxyl propyl methyl cellulose (HPMC) 1% (w/w)

PF-25/HPMC-3 :

Pluronic 25% (w/w) and hydroxyl propyl methyl cellulose (HPMC) 3% (w/w)

PF25-HPMC1-PE :

Pluronic 25% (w/w) and hydroxyl propyl methyl cellulose (HPMC) 1% (w/w) and PE formulation

References

  1. Rothbarth J, Bemelman WA, Meijerink WJ, Stiggelbout AM, Zwinderman AH, Buyze-Westerweel ME, et al. What is the impact of fecal incontinence on quality of life? Dis Colon Rectum. 2001;44(1):67–71.

    Article  CAS  Google Scholar 

  2. Whitehead WE, Borrud L, Goode PS, Meikle S, Mueller ER, Tuteja A, et al. Fecal incontinence in US adults: epidemiology and risk factors. Gastroenterology. 2009;137(2):512–7. e2

    Article  Google Scholar 

  3. Lee KJ. Treatment of fecal incontinence. J Kor Med Assoc. 2012;55(1):31–6.

    Article  Google Scholar 

  4. Badvie S, Andreyev H. Topical phenylephrine in the treatment of radiation-induced faecal incontinence. Clin Oncol. 2005;17(2):122–6.

    Article  CAS  Google Scholar 

  5. Park J-S, Kang S-B, Kim D-W, Namgung H-W, Kim H-L. The efficacy and adverse effects of topical phenylephrine for anal incontinence after low anterior resection in patients with rectal cancer. Int J Color Dis. 2007;22(11):1319–24.

    Article  Google Scholar 

  6. Baek C, Han M, Min J, Prausnitz MR, Park J-H, Park JH. Local transdermal delivery of phenylephrine to the anal sphincter muscle using microneedles. J Control Release. 2011;154(2):138–47.

    Article  CAS  Google Scholar 

  7. Jun H, Han M-R, Kang N-G, Park J-H, Park JH. Use of hollow microneedles for targeted delivery of phenylephrine to treat fecal incontinence. J Control Release. 2015;207:1–6.

    Article  CAS  Google Scholar 

  8. Jeong H-R, Lee H-S, Choi I-J, Park J-H. Considerations in the use of microneedles: pain, convenience, anxiety and safety. J Drug Target. 2017;25:29–40.

    Article  CAS  Google Scholar 

  9. Wang PM, Cornwell M, Hill J, Prausnitz MR. Precise microinjection into skin using hollow microneedles. J Invest Dermatology. 2006;126(5):1080–7.

    Article  CAS  Google Scholar 

  10. Kim Y-C, Park J-H, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliver Rev. 2012;64(14):1547–68.

    Article  CAS  Google Scholar 

  11. Schipper P, van der Maaden K, Romeijn S, Oomens C, Kersten G, Jiskoot W, et al. Repeated fractional intradermal dosing of an inactivated polio vaccine by a single hollow microneedle leads to superior immune responses. J Control Release. 2016;242:141–7.

    Article  CAS  Google Scholar 

  12. Dul M, Stefanidou M, Porta P, Serve J, O'Mahony C, Malissen B, et al. Hydrodynamic gene delivery in human skin using a hollow microneedle device. J Control Release. 2017; https://doi.org/10.1016/j.jconrel.2017.02.028.

    Article  CAS  Google Scholar 

  13. Kalluri H, Choi S-O, Guo XD, Lee JW, Norman J, Prausnitz MR. Evaluation of microneedles in human subjects. In: Dragicevic N, Maibach HI, editors. Percutaneous Penetration Enhancers Physical Methods in Penetration Enhancement. NewYork: Springer; 2017. pp. 325–340.

    Chapter  Google Scholar 

  14. Martin C, De Baerdemaeker A, Poelaert J, Madder A, Hoogenboom R, Ballet S. Controlled-release of opioids for improved pain management. Mater Today. 2016;19(9):491–502.

    Article  CAS  Google Scholar 

  15. Pathak P, Nagarsenker M. Formulation and evaluation of lidocaine lipid nanosystems for dermal delivery. AAPS PharmSci Tech. 2009;10(3):985–92.

    Article  CAS  Google Scholar 

  16. Katayoun D, Mahtab F, Seyedalireza S. Thermosensitive Pluronic® hydrogel: prolonged injectable formulation for drug abuse. Drug Des Devel Ther. 2010;4:255–62.

    Google Scholar 

  17. Chang JY, Oh Y-K, H-g C, Kim YB, Kim C-K. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm. 2002;241(1):155–63.

    Article  CAS  Google Scholar 

  18. Kabanov AV, Batrakova EV, Miller DW. Pluronic® block copolymers as modulators of drug efflux transporter activity in the blood–brain barrier. Adv Drug Deliver Rev. 2003;55(1):151–64.

    Article  CAS  Google Scholar 

  19. Jeong B, Kim SW, Bae YH. Thermosensitive sol–gel reversible hydrogels. Adv Drug Deliver Rev. 2012;64:154–62.

    Article  Google Scholar 

  20. Gupta J, Felner EI, Prausnitz MR. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol Ther. 2009;11(6):329–37.

    Article  CAS  Google Scholar 

  21. Kim E-Y, Gao Z-G, Park J-S, Li H, Han K. rhEGF/HP-β-CD complex in poloxamer gel for ophthalmic delivery. Int J Pharm. 2002;233(1):159–67.

    Article  CAS  Google Scholar 

  22. Moore T, Croy S, Mallapragada S, Pandit N. Experimental investigation and mathematical modeling of Pluronic® F127 gel dissolution: drug release in stirred systems. J Control Release. 2000;67(2):191–202.

    Article  CAS  Google Scholar 

Download references

Acknowledgments and Disclosures

This research was supported by a grant of Basic Science Research Program (2014R1A1A2A16051484) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education and by Industrial Strategic Technology Development Program (10,067,809, Development of vaccine formulation and patient-convenient vaccine microneedle) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

Author information

Authors and Affiliations

  1. Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Geonggi-do, Seongnam, 461-701, South Korea

    Hyunji Lee & Jung-Hwan Park

  2. Department of Internal Medicine, Kangbuk Samsung Hospital, and College of Medicine, Sungkyunkwan University, Seoul, South Korea

    Jung Ho Park

Authors
  1. Hyunji Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung-Hwan Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jung Ho Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jung-Hwan Park or Jung Ho Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, H., Park, JH. & Park, J.H. Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature Hollow Microneedle for Treatment of Intermittent Fecal Incontinence. Pharm Res 34, 2809–2816 (2017). https://doi.org/10.1007/s11095-017-2261-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-017-2261-9

Key Words

Search

Navigation