Nanotechnology Driven Herbal Medicine for Burns: From Concept to Application

By Md. Abul Barkat, Sarwar Beg and Farhan Jalees Ahmad

Burns can cause life-threatening injury and the lengthy hospitalization and rehabilitations required in burn therapy lead to higher healthcare costs. The risk of infection has also been one of the important concerns of burn wound management. The purpose of the burn wound care management is speedy wound healing and epithelization to limit the infection. The topical application of therapeutic agents is quintessential for the longevity of patients having significant burns. In recent times, research on herbal medicine for burn wound management has been vastly increased because of their safer toxicological profiles in contrast to synthetic medicines. Despite the promising therapeutic potential of herbal medicines in this area, herbal medications have some limitations which include low pharmacological activity, solubility and stability. Nanotechnology-based smart drug delivery approaches which involve the use of small molecules as nanocarriers, however, can help to overcome these biopharmaceutical challenges. This book provides an overview of plant-mediated metallic nanoparticulate systems and nanophytomedicine based therapeutic treatment modalities for burn wound lesions. Nine chapters deliver updated information about nanomedicines for burn wound therapy. Contributions are written by experts in nanomedicine and phytomedicine and collectively cover the pathophysiology of wound lesions, current and future outlook of nanomedicine based treatments for burn wound lesions, the role of biocompatible nanomaterials in burn wound management, plant-mediated synthesis of metal nanoparticles for treating burn wound sepsis, phytomedicine based nanoformulations and the phyto-informatics models involved in the wound healing process which are used to select appropriate nanotherapeutic agents. This reference serves as an accessible source of information on the topic of nanomedicine for burn treatments for all healthcare professionals (medical doctors, nurses, students trainees) and researchers in allied fields (pharmacology, phytomedicine) who are interested in this area of medicine.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Dec 29, 2021
• ISBN: 9789815039597

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Current Status and Future Outlook of Nanotechnology-Based Therapeutic Treatment Modalities for Burn Wound Management

Rana Mazumder¹, Subhabrota Majumdar², *

¹ Department of Pharmaceutics, Gitanjali College of Pharmacy, Lohapur-731237, Nalhati, Bi- rbhum, West Bengal, India

² Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology & AHS, Ba- nitabla, Uluberia-711316, Howrah, India

Abstract

In this chapter, we have highlighted most of the recent nanotechnology-based therapeutic treatment for burn wound management, considering the feasibility and appropriateness of each therapeutic procedure, and recovery of the injured tissue ultimately. A wide variety of these burn-deaths occur in small- and medium-wage countries, where survivors face an existence of morbidity. The availability of microbial nutrients, interference of the skin barrier, destruction of vascular supply in burns, along with critical immunosuppression are vital parameters that reduce burns resistance against the disease. Nanotechnology has provided a range of molecular designed nanostructures that can be used in both corrective and demonstrative burn applications. These nanostructures (NS) can be divided into organic and inorganic, such as polymer nanoparticles and silver nanoparticles, individually. This assessment covers the physiology of the skin, the classification of burns, the pathogenesis of burns, and different topical methodologies for combating contamination and stimulating healing. These incorporate biological methodologies dependent on antimicrobial and ultrasound treatment, as well as nanotechnology-based wound healing approaches as an advanced area of therapeutic approach. In this way, we have focused on an organic and inorganic nanostructure designed to give advanced formulation for the burned skin, their management/treatment etc. The injury recovery process is a characteristic and unpredictable reaction of the body to its injuries and incorporates a highly coordinated arrangement of biochemical and cellular phenomena to restore the respectability of injured skin and tissues. The nature and related complications of burns lead to inadequate and delayed recovery from these types of injuries. Among the various materials and structures that have been used in wound management, useful nanotechnology-based structures demonstrated an incredible opportunity to enhance the repair procedure of various types of wounds. The aim of this research is to give an illustration of the on-going reviews on nanotechnology-dependent burn wound management and the future view of these frameworks here.

Keywords: Antimicrobial, Burn Wounds, Burn Injuries, Burns Classification, Cellular Phenomena, Microbial Nutrient, Nanotechnology, Nanostructures, Polymeric Nanoparticles, Pathogenesis, Skin Wounds, Silver Nanoparticles, Wound Healing, Wound Disease.

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* Corresponding author Subhabrota Majumdar: Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology & AHS, Banitabla, Uluberia-711316, Howrah, India;

Tel: [phone]; E-mail: [e-mail]

INTRODUCTION

The skin is the biggest part of the body, acts as an essential obstacle with immune, sensory and defensive capacity. The external condition of the skin is exposed against different external elements that cause various types of skin damage and lesions [1]. The injury is the after effect of a disruption of typical functional structure and capacity, influencing deep core tissues, causing irritation and contamination. Huge numbers of patients experience the pernicious effects of defenseless injury repair, which is considered the main source of death. Ignored injury management can lead to genuine contaminations, longer stays in the emergency clinic, mutilation, and markedly decreased overall vital function [2].

A burn is a physical characteristic of the skin or tissue problem caused on a very basic level by heat or radiation, radioactivity, disintegration, or connection with artificial substances. Wounds to the skin due to high radiation, radioactivity, or man-made substances, along with respiratory damages due to internal breath from smoke, are also the cause of burns. In the most recent report released by the WHO, it is expected that more than 0.2 million people’s deaths, even though it all happens every year, as an immediate consequence of burns [3-5].

The skin is the most dynamic part of the body. The use of a powerful antimicrobial treatment is an important methodology to initiate injury recovery and promote repair. Most efforts have been made using the antimicrobial treatment of a wide variety of topical applications for the therapeutic process, promoting disinfection in affected areas, along with the improvement of injury repair procedures and tissue recovery steps. Most infection occurs due to outburst of the infection to the outer regions of the body [6-10].

Acute wounds are generally characterized by reduced microbial infection, scab formation, infiltration of the immune cell and early invulnerable cell penetration, while recovery is related to re-epithelialization, angiogenesis, and fibroblast relocation. This is reflected in the development of microbial colonies and the appearance of some biochemical processes, for example, major location signals. If the immune system cannot control the infection, progression of the microbial biofilms is developed and the injury becomes a progressive wound. Chronic infection is described by an expanded inflammation procedure, lower deep tissue oxygenation due to the formation of fibrin, fibroblast aging, weakened angiogenesis, and delayed re-epithelialization. Recent injury recovery treatments for most components do not give a decent clinical result, either fundamentally or practically. Therefore, nanotechnology, through its flexible physicochemical properties, is a robust examination area for wound recovery treatments [11].

The present chapter provides a brief outline of skin structure, physiology of the burn wound, burn wound healing, conventional treatment available for burn wound management, and advancement in nanotechnology to effectively deal with burn against subsequent infections. Furthermore, this section addresses the difficulties and opportunities provided by monomolecular delivery of the drug, giving skin morphogenesis in burn wound management.

Skin

In general, the skin is produced by three layers named as epidermis, dermis, and hypodermis [12]. The epidermal part is made up of five layers known as Stratum basale, Stratum spinosum, Stratum granulosum, Stratum lucidum and Stratum corneum respectively [13]. These layers contain various immune and non-immune cells [14-16]. The basal part is basically a proliferative segment of the epidermis, which produces keratinocytes that can separate by the spinosum part, granular layer and layers of the corneum. The dermal layer is mainly a portion between the hypodermis and epidermis layers. It is composed of collagen proteins, blood vessels, sweat glands, roots of the hair, nerve cells, vessels of lymphatic cells, and stem cells of mesenchyma [17, 18]. The principal function of the dermis is to give auxiliary hardness to the skin. The subcutaneous fat is composed of adipose cells, macrophages, vasculature, nerve cells and fibroblasts, which are protected dermis and epidermis layers [19].

Physiology for Burn Wounds

Skin injury from burns can be best described by the gravity of the thermal burn and the stages of the burn [20]. The stages of the thermal burns on the skin are illustrated in Fig. (1). The thermal burn from dry sources and wet sources represents all of the burns [21] and can be characterized depending on the gravity of the burn [22, 23]. Despite being close to the place of the burn injury, a severe heat injury, more in a huge area of the skin, causes intense fundamental reactions, all known as burn shock [24]. Burn shock is described by fine expanded porosity, expanded hydrostatic weight on the microvasculature, protein along with smooth effort from the intravascular gap to the interstitial gap, expanded vascular opposition, decreased cardiovascular performance, and hypovolemia requiring fluid reactivation [25].

Fig. (1))

Schematic presentation of thermal burns.

The epidermis is the peripheral layer that fills up as a defensive boundary of the skin against external hostilities and maintains hydration and recovery of the skin. The dermis is a strong network provided by collagen, elastin, nerve structures, skin, limbs, and connective tissue [26], offering auxiliary support, glandular capacity, and a water system [27].

On-going hypermetabolism and inflammation weaken the recovery process through delayed re-epithelialization [28, 29]. The degree of inflammation and hypermetabolism is identified with the degree [30] and the depth of consumption, as deeper ingestions show higher levels of cytokines [31] and a more marked hypermetabolic reaction [32]. Essentially, the degree of consumption is an effective indicator of the length of stay in the clinic [33] and mortality [34].

The skin consistency is damaged by injury; a therapeutic reaction occurs for skin repair, including the four phases through haemostasis, inflammatory phase, Proliferative phase and maturation. In the main stage, vasoconstriction, platelet accumulation, and adherence of platelets into a plug occur, which initiates the development of clotting. At a similar time, irritation sets in, as fibrin clotting secretes cytokines and developmental factors that trigger the quantity of neutrophils followed by macrophages (separate lymphocytes and monocytes) to the lesion. This causes the formation of oxygen species accessions, and proteinases secure the body against exogenous microorganisms. Cytokine release will advance to a third stage, which maintains cell expansion, angiogenesis, tissue granulation and, finally, advances the improvement of a transient extracellular network. This regenerative procedure is possibly hampered by diseases, which can be infectious or bacterial in origin, the most predominant microorganisms being Staphylococcus aureus (gram-positive organisms), Pseudomonas aeruginosa (gram-negative microbes) [35, 36], and Candida spp. (Parasites) [37]. After a depletion injury, with the warm extinction of the skin and the haemostasis stage, the exterior of the depletion wound appears as a necrotic vascular tissue with high protein content, causing the movement of insusceptible cells.

As per the model, the burn can be differentiated into three regions, depending on the tissue extinction [38-41]. The central portion of the injury is identified as the coagulation region as it has the most intimate contact with the heat source. Denaturation of proteins occurs at above 41°C, whereby extreme heat at the injury site causes extensive coagulation, denaturation, and protein corruption to the tissue site. The coagulation region of ischemia is described by reducing perfusion and possibly recoverable tissue. There, ischemia and hypoxia can lead to tissue rot within 48 hours after injury without medical procedure [42].

Different investigations have indicated that apoptosis is dynamic up to 30 minutes after the burn [43] depending on the strength of the burn injury [44]. It could be assumed that oxidative pressure improves necrosis, as preclinical trials have established promising reductions in putrefaction with the organization of key agents for cancer prevention [45]. Although burns are not exactly the same as different injuries in certain respects, for example, the fundamental level of aggravation, recovery from all injuries is a single procedure with stages of coverage [46, 47].

In this way, the proliferative phase is described by the description of keratinocytes and fibroblasts with cytokines and developmental factors [48]. Here, the keratinocytes are transferred above the injury to help complete reconstruction of the vascular system, which is an acute advance in the burn injury recovery process [49]. This correspondence is organized by the endothelial, stromal, and invulnerable cells that decide the path of repair, including completion along with revascularization.

Burn Wound Healing

Thermal burns caused by fire represent ~80% of each of the burns reported and can be classified by the intensity of the fire. Despite the local wound on the side of the affected site, severe thermal damage to the skin leads to an acute systemic reaction known as burn shock. Burn shock is classified by improved capillary permeability, improved hydrostatic pressure through the microvascular, movement of proteins and fluids from the intravascular part to the transition space, improved systemic vascular resistance, condensed cardiac output, and hypovolemic requiring fluid recovery. Edema is an interstitial structure that grows rapidly in the first 8 hours after burns and continues to develop more slowly for 18 hours. Additional factors affecting these include non-occurrence of an inhalation injury, recurrence of complete burns, and injury. The actual inserting flow rate is assessed hourly in view of the sufficiency of physiological reactions, e.g., urine output [50]. Burn represents a particular wound entity with exceptional clinical characteristics. Jackson first described three burning zones:

A. Coagulation zone: The zone of greatest impact is at the focal point of the injury. Denaturation, coagulation of component proteins and damage of plasma film are observed with visible necrosis at the focal point of the lesion.

B. Zone of stasis: In the adjacent region of stasis, a cooperated tissue perfusion can possibly be observed, ranging from vital capillary vasoconstriction to ischemia. This region can be easily altered into necrosis by the cumulative property of reduced perfusion, edema, and contamination. However, when accurately managed, these changes can be preserved.

C. Zone of hyperemia: The outer part of the burn injury represents the region of hyperemia categorized by viable cells and vasodilation mediated by general inflammatory mediators. Tissue surrounded by this zone generally recovers fully unless it is dense from contamination or severe hypoperfusion. Tissue failure in the adequate coagulation zone to direct heat induces protein denaturation, particularly the stasis region, and additional hyperemia contributes to the overall burn wound pathology. A powerful activation of poisonous inflammatory mediators, like as oxidants and proteases, damages the skin and capillary endothelial cells, thus disturbing the severity of the trauma and promoting ischemic tissue necrosis [51].

NANOMEDICINE AND ADVANCEMENT IN THERAPY FOR BURN WOUND MANAGEMENT

Metallic Nanoparticles

Metallic nanoparticles have been exploited for different purposes, which have been covered as a useful material to treat burns and their infections [52]. Silver substances have been utilized to treat burns. The ionized silver compound (Ag+) can respond with thiol and protein residues in microbial cells, limiting the growth and metabolism of microorganisms. Silver also heals the damaged layer and disturbs electrical conductivity with the membrane potential [53]. Silver nitrate was the first unique burn substance used to hinder the growth of microorganisms. The antimicrobial features of silver are owing to the ability to improve the plasma membrane, which changes penetrability and leads to lysis of the organism [54].

Copper constituent and its derivatives like as the Copper-nitrate complex have antimicrobial properties [55]. Copper ions attach to a few essential parts of the microorganism and restrain their enzymes. Copper salts have been used in infected skin burns [56].

Gallium is a hard constituent that is not originated in its pure form in nature, whereas its ionic form Ga³+ has been found in many minerals like as, aluminium and zinc. Ga³+ substances have been revealed to have antimicrobial action. An additional metallic constituent is ferric iron (Fe³+) which is a very important constituent in bacterial expansion and metabolic pathways [57].

Halogen-based substances have been utilized as antimicrobial agents. Hypochlorous acid is a chlorine substance that is able to destroy DNA and inactivate oxidative phosphorylation catalysts in microorganisms. It has a promising effect and disrupts virus nuclei, capsids and also be used to disinfect contaminated burns [58]. Iodine molecules restrain the vital enzymes of germs by essential to the sulphur groups of their proteins [59]. Iodine compounds have been applied as antiseptics and disinfectants for the management of burn infection [60, 61].

Polymeric Nanoparticles

The capability of polymeric nanoparticles to penetrate skin layers depends on their compound, the size of the molecule, and the consistency of the preparation [62]. Chitosan has been extensively concentrated in this field. They are prepared by the soluble deacetylation technique of chitin [63]. Chitosan is non-poisonous, biocompatible, biodegradable [63] with antimicrobial activity, low immunogenicity that has been related to the capacity to advance wound healing by the act to fibroblasts, macrophages, and polymorph nuclear leukocytes [64]. Ding et al. portrayed the cross-linking of chitosan with genipin by the expansion of mostly oxidized polysaccharides to set up another biomaterial for wound treatment [65]. El-Feky et al. portrayed silver loaded sulfadiazine in chitosan nanoparticles go about as a dressing for the treatment of burn wounds [66]. The combination of chitosan and melatonin advanced wound epithelialization for the creation of nanoparticles.

Liposomal Nanoparticles

Liposomal nanoparticles comprise of spherical vesicle prepared of as a minimum one or more lamellar lipid bilayers. An investigation detailed to facilitate dihydroquercetin defined as a liposomal nanocomplex could improve endogenous cancer prevention agent movement, decrease the necrotic region on burn skin and ultimately stimulate better recuperating [67].

Solid lipid nanoparticles are at room temperature solid colloidal medication conveyance vehicles prepared by solid lipids instead of the liquid lipids utilized in nanoemulsion. Solid lipid nanoparticle (SLN) prepared by round solid lipids can incorporate in hydrophilic molecules. In a study, Sandri et al have formulated SSD-loaded solid-lipid nanoparticles and tested for delayed release and to decrease pain in extreme skin infections. Moreover, the use of SLN expanded cell movement and improved wound rates [68]. In other research, SLN loaded by nitrofurazone went about as a conveyance vehicle to carry the skin medication to the burn which improves the antimicrobial action of nitrofurazone for the management of sepsis in burn wound patients [69]. The second generation of SLN called as nanostructure lipid carriers which are comprised of solid and fluid parts given better stability [70, 71].

Nanoemulsion

Nanoemulsion comprises a heterogeneous arrangement of two immiscible fluids balanced out by an appropriate surfactant [72]. Nanoemulsion is a simple and isotropic spreading that has numerous advantages since they are neither poisonous non-irritant [73], it very well may be incorporated into different kinds of pharmaceutical formulations [74] with long term physical stability [75]. Bonferoni et al. [76] described that tocopherol loaded nanoemulsion made by chitosan oleate used for the management of skin wounds. Chitosan with oleic acid are well-known for their valuable outcomes on wound healing. Song et al. assessed the antibacterial and hostile to biofilm movement of a chlorhexidine acetic acid derivation nano emulsion against methicillin-resistant Staphylococcus aureus diseases impervious to skin burns [77].

Nanogels

Nanogels consist of hydrogels comprised of particles inside the nanometer range [78]. Hydrogels are three-dimensional cross-connected polymer organizes and be able to assimilate a lot of water or natural liquid [79]. Nanogels are biocompatible and inhibit enzymatic degradation of the medication. Chitosan-alginate based silver sulfadiazine loaded nanogels have more helpful viability in burns [80]. Nanohydrogel gellen-cholesterol based surrounded baicalin was introduced for wound remedial process [81]. Nanohydrogel loaded by baicalin exhibited the best performance for skin restoration which was inhibited the inflammatory cell [82]. It was found that a newly bacterial cellulosic nanocrystal hydrogel could quickly maintain the activity and human morphology of dermal fibroblasts. This hydrogel was proving a major function in skin regeneration. Nanohydrogel based on natural polysaccharide injectable was also reported as the best formulation for