Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Journal of Controlled Release (Impact Factor: 7.71). 08/2007; 120(3):178-85. DOI: 10.1016/j.jconrel.2007.04.016
Source: PubMed


Peritoneal adhesions are tissue connections that form within the abdominopelvic cavity following surgery or other injuries. They can cause major medical complications. Barrier devices and pharmacological agents have been used to prevent adhesion formation, with mixed success. We hypothesize that an adhesion barrier which also delivers anti-adhesion drugs can address both physical and physiological causes for adhesion formation. Here, we describe an in situ cross-linking hyaluronan hydrogel (barrier device) containing the glucocorticoid receptor agonist budesonide. Budesonide was chosen because of the known role of inflammation in adhesion formation, hyaluronan because of its known biocompatibility in the peritoneum. The system, consisting of two cross-linkable precursor liquids, was applied using a double-barreled syringe, forming a flexible and durable hydrogel in less than 5 s. We applied this formulation or controls to the injured sites after the second injury in a severe repeat sidewall defect-cecum abrasion model of peritoneal adhesion formation in the rabbit. Large adhesions (median area 15.4 cm(2)) developed in all saline-treated animals. Adhesion formation and area were slightly mitigated in animals treated with budesonide in saline (median area 5.0 cm(2)) or the hydrogel without budesonide (median area 4.9 cm(2)). The incidence and area of adhesions were dramatically reduced in animals treated with budesonide in the hydrogel (median area 0.0 cm(2)). In subcutaneous injections in rats, budesonide in hydrogel reduced inflammation compared to hydrogel alone. In summary, budesonide in a hyaluronan hydrogel is easy to use and highly effective in preventing adhesions in our severe repeated injury model. It is a potentially promising system for post-surgical adhesion prevention, and suggests that the effectiveness of barrier devices can be greatly enhanced by concurrent drug delivery.

10 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the most common complications following abdominal surgery is the formation of postsurgical adhesions (PSAs). While often asymptomatic, these formations can result in numerous complications, including pain, infertility, and bowel obstructions, and can increase the difficulty of future surgeries. Various strategies have been developed to reduce the incidence of these adhesions, yet the most successful to date have been the use of physical barriers composed of biocompatible materials. Yet, despite the success of these materials, PSAs remain a significant clinical challenge. This chapter provides a summary of the field from a biomaterials perspective, an overview of the mechanism of PSA formation and a review of the technologies developed in attempting to reduce their occurrences, including the limitations that exist with each of these strategies. At the end of this chapter, a summary of the analytical methods used in assessing adhesion barrier performance and their limitations, and a call for more quantitative analytical materials performance characterization are presented.
    01/1970: pages 397-416;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A key component of any autonomous system is a decision module, which is capable of handling large volume of data at high speed and high reliability. This paper is focused, in the main, on the development of a decision module, which is capable of functioning in an environment of imprecision, uncertainty and imperfect reliability. There are two principal tasks: task A, which is aimed at the development of novel methods of analysis and design: and task B, which is focused on the development of a decision-support system for ranking of decision alternatives. Following is an outline of the principal issues, which is addressed in task A.
    Industrial Informatics, 2003. INDIN 2003. Proceedings. IEEE International Conference on; 09/2003
  • [Show abstract] [Hide abstract]
    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Annals of Surgery 03/2008; 247(4):712. DOI:10.1097/SLA.0b013e31816a4ea7 · 8.33 Impact Factor
Show more