Wound healing by enhancing cell proliferation: a thermoreversible formulation containing raloxifene
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Updated: May 8, 2025

Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
Published on: August 21, 2020
Subodh Kumar1, Yogesh Kumar Verma2
1Regenerative Biology Research Lab, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi, 110054, India.
Abstract:
The challenge of ineffective wound healing, leading to chronic conditions necessitates the development of novel therapeutics strategies. Currently, a plethora of ailments have been researched and marketed globally to accelerate angiogenesis, re-epithelization, collagen synthesis, and proliferation. However, clinical translation remains challenging and requires rigorous pre- and post-clinical screening. Here, we have developed a formulation encapsulating Raloxifene, a repurposed drug, aimed to induce accelerated wound healing. Four different formulations (Forms 1, 2, 3, and 4) incorporating alginate, poloxamer 407 (P407), LiCl, and fetal bovine serum were prepared. Formulations were characterized by scanning electron microscopy, Fourier Transformation infrared spectroscopy, and rheology. In vitro assessments encompassing cell viability, cell migration, and drug release profile were conducted, subsequently, the in vivo wound healing potential was evaluated in Sprague Dawley (SD) rats. In results, we observed significant (p-value<0.05) wound healing by Form 3 at 14th due to up-regulation of TGFꞵ, Col-I and GSK3β genes. The histology results showed complete development of epidermis, endoderm and collagen fibers by Form 3, leading to complete healing. This formulation shows promise for clinical application in accelerated wound healing processes.
Insights
A novel Raloxifene formulation (Form 3) significantly accelerated wound healing in rats by promoting tissue regeneration and collagen synthesis. This therapeutic strategy shows promise for clinical applications in managing chronic wounds.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Drug Repurposing
Background:
- Ineffective wound healing leads to chronic conditions, necessitating advanced therapeutic strategies.
- Current treatments aim to enhance angiogenesis, re-epithelialization, collagen synthesis, and cell proliferation, but clinical translation faces hurdles.
- Raloxifene, a repurposed drug, is explored for its potential in accelerating wound healing processes.
Purpose of the Study:
- To develop and characterize novel formulations for accelerated wound healing.
- To evaluate the efficacy of a Raloxifene-encapsulating formulation in promoting wound closure.
- To investigate the molecular mechanisms underlying the wound healing process induced by the formulation.
Main Methods:
- Four formulations (Forms 1-4) were prepared using alginate, poloxamer 407, LiCl, and fetal bovine serum.
- Characterization included scanning electron microscopy, Fourier Transform infrared spectroscopy, and rheology.
- In vitro (cell viability, migration, drug release) and in vivo (rat wound model) assessments were performed.
Main Results:
- Formulation 3 demonstrated significant wound healing by day 14 (p<0.05).
- Gene expression analysis revealed upregulation of TGF-β, Col-I, and GSK3β.
- Histological examination confirmed complete epidermal and dermal layer development with organized collagen fibers.
Conclusions:
- The developed Raloxifene formulation (Form 3) effectively accelerates wound healing.
- The mechanism involves the upregulation of key genes involved in tissue regeneration and collagen synthesis.
- This formulation holds significant potential for clinical translation in treating chronic wounds.
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