Development and evaluation of wound healing hydrogels based on a
quinolone, hydroxypropyl methylcellulose and biodegradable microfibres
Chukwuma O. Agubata
a,
⁎, Chiadikaobi Okereke
a
, Ifeanyi T. Nzekwe
b
, Remigius I. Onoja
c
, Nicholas C. Obitte
a,d
a
Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu State, Nigeria
b
Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria
c
Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Enugu State, Nigeria
d
Universitaet Greifswald, Institut fuer Pharmazie, Biopharmazie & Pharmazeutische Technologie, Felix-Hausdorff-Straße 3, C_DAT, 17489, Greifswald, Germany
abstract article info
Article history:
Received 28 January 2016
Received in revised form 10 March 2016
Accepted 14 April 2016
Available online 16 April 2016
Chemical compounds studied in this article:
Ofloxacin (PubChem CID: 4583)
Hydroxypropyl methylcellulose (PubChem CID:
57,503,849)
Ofloxacin is a synthetic antibiotic of the fluoroquinolone class, with activity against gram-positive and gram-
negative bacteria. Wound healing involves a complex interaction of cells and processes which can be improved
using appropriate wound- dressing materials. The aim of the present study was to develop and evaluate
wound healing hydrogels containing hydroxypropyl methylcellulose (HPMC), ofloxacin and biodegradable
microfibres from surgical sutures. The hydrogels were formulated by air-drying mixtures of dilute dispersions
of micronized sutures (polyglycolic acid, Vicryl® and catgut), ofloxacin and HPMC gel. The prepared hydrogels
were evaluated for gel fraction, swelling capacity, breaking elongation, particle size and morphology, and chem-
ical interactions. Furthermore, in vivo wound healing activities were studied in rats using excision wound model
and histological examination. The percentage gel fraction was ≥50% in all the batches, the percentage swelling
ratio was within the range of 531.8–1700% and the percentage breaking elongation was found to be in the
range of 70–120%. The chemical interaction studies using Fourier Transform Infra Red (FTIR) spectroscopy
showed that there was no interaction between the drug and excipients used. Ofloxacin-loaded hydrogels con-
taining dilute microfibres of the sutures showed 95% wound size reduction after fourteen days. These formula-
tions also caused high collagen deposition after twenty one days of wounding, with minimal scar formation.
Ofloxacin hydrogels containing HPMC and micronized suture fibres can be applied for effective wound healing.
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Polyglycolic acid
ofloxacin
sutures
1. Introduction
A wound can occur as defect or break in the skin, resulting from
physical, chemical, thermal damage or as a result of the presence of an
underlying medical or physiological condition. Wound healing is a nec-
essary response to tissue injury. It involves sequential steps of inflam-
mation and tissue repair, which are complex physiological processes
of epithelialization, formation of granulation tissues and tissue remodel-
ing (Evans, 1980). These complex processes of cellular and biochemical
interactions involve various cells such as keratinocytes, fibroblasts and
endothelial cells. The wound healing phases and their biophysiological
functions are expected to occur in the proper sequence, at specific
times, and progress for a specific duration at an optimal intensity
(Mathieu et al., 2006). Energy, carbohydrate, protein, fat, vitamin, and
mineral metabolism all can affect the healing process (Arnold and
Barbul, 2006).
Wound dressings are expected to maintain a moist environment
around the wound and absorb the exudates from the wound surface
(Turner, 1979). Hydrogels swell upon hydration without dissolving
and can provide the necessary trapped moisture for effective wound
healing. Hydroxypropyl methylcellulose (Hypromellose) exhibits a
thermal gelation property in an aqueous solution. When the gel solution
heats up to a critical temperature, the solution congeals into a non-
flowable but semi-flexible mass.
Hydrogels with large water content are highly biocompatible and
possess mechanical properties similar to those of soft tissues and this
allow the incorporation of cells and bioactive molecules during the gel-
ling (Drury and Mooney, 2003; Nguyen and West, 2002). However, al-
though cells do not readily attach to highly hydrophilic surfaces like
hydrogels, the bulk or surface chemistry of hydrogels can be easily mod-
ified with extracellular matrix (ECM) domains, which promote cell ad-
hesion (Seliktar, 2005).
The incorporation of biodegradable suture materials in hydrogels
may provide domains that could promote cell adhesion, tissue regener-
ation and wound healing. A form of biodegradable scaffold may be cre-
ated. Bio-composite formulations have been developed with synergistic
wound healing outcomes (Perumal et al., 2014). Furthermore, in order
to prevent contamination of wound, an anti-infective agent would be
necessary. Ofloxacin is a synthetic antibiotic of the fluoroquinolone
class. Ofloxacin is a broad-spectrum antibiotic that is active against
both Gram-positive and Gram-negative bacteria. It functions by
European Journal of Pharmaceutical Sciences 89 (2016) 1–10
⁎ Corresponding author.
E-mail address: chukwuma.agubata@unn.edu.ng (C.O. Agubata).
http://dx.doi.org/10.1016/j.ejps.2016.04.017
0928-0987/© 2016 Elsevier B.V. All rights reserved.
Contents lists available at ScienceDirect
European Journal of Pharmaceutical Sciences
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