Sterile thermoresponsive formulations for emergency management of burns
Introduction
Management of burn injuries are highly challenging as significant fluid loss and extensive tissue damage impair vital skin functions. Local tissue damage as a result of infection leads can make victims susceptible to life- threatening sepsis and multiple organ failure. Delayed and painful healing, infection, discomfort, and hyperplastic scars continue to challenge health care professionals [1], [2], [3], [4]. Minor burns can be treated with suitable medical care and dressings, avoiding the need for an intensive review or surgery. Major injuries are a cause of concern because the impact of scar tissues on the body is devastating, and only plastic surgery procedures can minimize deformity and restore the appearance of the tissues[5], [6]. The outcomes of burn patients are determined by the severity and degree of the burn and the care given to burn victims immediately after they sustain burns can have a significant impact on the extent and depth of the wound. Bystanders are frequently the first responders to burn injuries. The initial phase of first aid is pre-hospital care starting with the accident scene and culminating with specialized/institutional help. Thus, we need to have products that are readily available, easy to use, and stop the progression of the injury without hampering medical care carried out at a later stage. Prompt pre-hospital care delivered in an effective and systematic manner can reduce the progress of burns, thereby minimizing morbidity [7], [8].
Thermo-responsive polymers respond to changes in body temperature and can be considered as potential polymers in wound dressings [9], [10], [11], [12], [13], [14]. These polymers exhibit sol–gel transition on reaching a critical temperature, thus undergoing a modification in their physicochemical and mechanical properties [10], [14], [15], [16], [17]. They are biodegradable, biocompatible, non-irritating and adheres to mucous membranes [18].
Calcium is primarily involved as Factor IV in the hemostatic phase of wound repair, and as a modulator for epidermal cell migration and regeneration in subsequent stages of healing [19]. Many studies have proven that calcium dressings improve the healing process by mediating the movement of ionized calcium through the wound bed [1], [20], [21].
According to reports, infection is the foremost cause of burn injury related morbidity and mortality and patients are susceptible to infection at the time of injury and during the healing process [22], [23]. Since time immemorial, copper has been recognized as a powerful antimicrobial. Copper has a broad spectrum biocidal effect on bacteria, including Methicillin-resistant Staphylococcus aureus, and Vancomycin resistant Enterococci, fungi, and viruses, according to laboratory studies. Several clinical studies have evaluated the use of copper surfaces in the hospital setting, with significant reductions in bacterial count on copper surfaces when compared to other standard antimicrobials [24]. Metal oxides like silver oxide, zinc oxide, copper oxide, magnesium oxide and calcium oxide are reported to possess antimicrobial and wound healing properties [25], [26], [27], [28], [29], [30], [31], [32].
The proposed formulation is a sterile, aqueous, isotonic dispersion which can be used as an emergency aid for burn patients. This solution can be poured on the open surface of burn injury (second or third degree), without touching the victim and preventing undue trauma to the patient. The solution can be applied warm (body temperature) or cold on the burns. On contact with body temperature, a thin layer of gel is formed at the site of application. This product could make it to a part of the first- aid kit wherever fire hazards are expected. They do not require daily removal and can be left in place until healing is complete. This can ease pain and mitigate the trauma associated with frequent change in dressing. The formulation can be packed in PVC bags or bottles and will be useful as an irrigation gel forming liquid which can cover even inaccessible areas of second and third degree burns.
All formulations contained nano calcium sulphate (promotes rapid healing and aids in tissue regeneration)[1], [21], nano copper oxide (promotes angiogenesis and skin extra cellular matrix formation), varying concentrations of poloxamer 40 and chitosan, 0.12 % of soy lecithin (to maintain tissue hydration and aid in tissue repair [33], [34]), 0.9 % of sodium chloride (maintains isotonicity), and 1 % glycerol (humectant that absorbs exudate from wounds and prevents its pooling in areas surrounding the wound).
Section snippets
Materials
Chitosan was procured from Marine Chemicals, India. Calcium sulphate, soy lecithin, poloxamer were procured from Yarrow Chem Products, India. Glycerol was purchased from Loba chemicals, India. Culture media for sterility testing was procured from Himedia Laboratories ltd., India.
Preparation of nano calcium sulphate (NCS) and nano copper oxide (NCuO)
0.7 % Calcium sulfate was dispersed in water and probe sonicated (QSONICA, CL-334, India) for 15 min to obtain a uniform dispersion, poured into Petri plates, and dried in a tray dryer (Ti-130FAC, India). The particles
Determination of particle size distribution and polydispersity index
Average diameter and polydispersity index of NCS particles as determined by DLS was 220.7 nm and 0.005 respectively. The diameter and polydispersity of NCuO was found to be 273.3 nm and 0.245 respectively (Fig. 1).
Analysis of elemental composition
The elemental composition of the formulations incorporated with NCuO and NCS was determined by SEM-EDX. The peaks clearly denote the presence of calcium and copper ions (Fig. 2).
pH determination
pH is a crucial determinant for effective wound healing, and studies have demonstrated that the environment
Conclusions
In the present study, we described the development of sterile thermo responsive formulations for burn management. The formulations containing nano calcium sulphate nano copper oxide along with thermo-responsive polymers were capable of gelling when in contact with the burnt area, thus forming a protective layer over the affected area. The presence of nano calcium sulphate and nano copper oxide was responsible for healing and prevention of infection during the course of treatment. The authors
CRediT authorship contribution statement
Darshan Ramesh: Investigation. Sindhu Abraham: Conceptualization, Methodology, Data curation. Megha Krishnappa: Investigation. Bharath Srinivasan: Writing – review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The authors would like to thank Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences for supporting this project by providing necessary facilities. The authors thank Micro and Nano Characterization Facility (MNCF), Centre for Nano Science and Engineering (CeNSE), Indian Institute of Science, Bengaluru for extending instrumentation facilities to conduct ZetaPALS and SEM-EDX studies. The authors also wish to thank Koushik Laboratory for the histopathological analysis.
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