J Crit Rev, Vol 2, Issue 2, 12-20 Review Article


NOVEL DRUG DELIVERY STRATEGIES AND APPROACHES FOR WOUND HEALING MANAGEMENTS

FEDELIC ASHISH TOPPO, RAJESH SINGH PAWAR

Pharmacognosy and Phytochemistry Laboratory, Faculty of Pharmacy, VNS Group of Institutions, Neelbud, Bhopal, Madhya Pradesh, India 462044
Email: ashish_two@yahoo.co.in  

Received: 05 Mar 2015 Revised and Accepted: 10 Apr 2015


ABSTRACT

New ideas on controlling the pharmacokinetics, pharmacodynamics, non specific toxicity, immunogenicity, biorecognition and efficiency of drugs have generated new strategies, often called as the drug delivery system. Evolution of an existing drug molecule from a conventional form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety, and efficacy. Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) from synthetic and natural bioactives such as polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes have been reported. The variety of dressings based on types of wounds and novel polymers used for the delivery of drugs to acute and chronic wound has resulted in a wide range of new products frequently introduced to target different aspects of the wound healing process. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. Nevertheless, nanofibers with their physicochemical properties and nanotopography display improvements in the fields of tissue engineering, wound therapy and drug delivery systems. At present, there are so many existing drug delivery technologies that a total compilation is not within the scope of this article. Yet an attempt is being made to compile some of the most successfully marketed drug delivery technologies. This review extends the information and hopes to give insight into past, present and future strategies and approaches for wound healing managements.

Keywords:Drug delivery systems, Novel drug delivery, Wound, Wound healing management.


INTRODUCTION

Novel drug delivery system is largely based on promoting the therapeutic effects of a drug and minimizing its toxic effects by increasing the amount and persistence of a drug in the vicinity of the target cell and reducing the drug exposure of non target cells [1]. Novel formulations are reported to have remarkable advantages over conventional which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. Development of novel drug delivery systems (NDDS) from synthetic and natural bioactives such as polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported. Nanoparticles and nanoformulations have already been applied as drug delivery systems with great success; and nanoparticulate drug delivery systems have still greater potential for many applications [2].

The skin is a complex organ with three distinct histological layers: the epidermis, the dermis, and the hypodermis. Wound healing of healthy skin is an immediate restorative response to injury [3], and the process is dependent on unipotent and multipotent stem cells that reside in the basal layer of the epidermis, the hair follicle bulge, the sebaceous glands at the base of the hair follicle, the dermal papillae, and the dermis [4-6].

According to the Wound Healing Society, a wound is the result of ‘disruption of normal anatomic structure and function [7]. Wound healing progresses through a series of interdependent and overlapping stages in which a variety of cellular and matrix components act together to reestablish the integrity of damaged tissue and replacement of lost tissue [8, 9]. The wound healing process has been reviewed and described by Schultz [10] as comprising five overlapping stages that involve complex biochemical and cellular processes. These are described as haemostasis, inflammation, migration, proliferation and maturation phases. In fact, Cooper [11] has argued for expanding the understanding of wounds beyond the cellular level to a molecular context as well. He emphasized the need to approach wound healing at multiple levels (cellular and molecular) to help improve wound treatment and management. In the developed countries, many sophisticated dressings are available to the wound care practitioners which are made from a wide range of materials including polyurethane, salts of alginic acid and other gel able polysaccharides such as starch and carboxymethylcellulose. These materials are combined to form products as diverse as films, foams, fibrous products, beads, hydrogels and hydrocolloid dressings [12] (table 1). The situation is totally different in the developing countries like ours where what is still commonly available to wound care provider are traditional agents such as sodium hypochlorite, hydrogen peroxide, cetrimide solution, chlorhexidine and others. These agents have been proven to be of limited efficacy and may also have an adverse effect upon the healing process [13] and therefore get out of favour [14]. Wound management methods depend on the healing process, the status and living environment of the patient, and the physical/chemical properties of the wound. Therefore, there is much attention given to the study of the physical characteristics and clinical role of available dressings with respect to each wound treatment phase and wound type [15, 16]. Wound related factors takes priority when considering choice of dressing for a particular wound. Therefore, we should always ask ourself, what type of wound are we dealing with? Is it a superficial, full thickness or cavity wound? Is the wound necrotic, sloughy, and granulating or epithelising? What about its characteristics, is it dry, moist, heavily exuding, malodorous, excessively painful or liable to bleed? What about the bacterial profile, is it sterile, colonized or infected? For example, a superficial, granulating or epithelising wound with minimal exudate should not be dressed with agents like hypochlorite solution or hydrogen peroxide. Rather, such wound may be dressed with sofra-tulle covered with saline soaked gauze or even dry gauze. In clinical practice, when considering dressings for an acute wound, the emphasis should be on prevention of infection and promotion of healing [17] whereas in chronic wound-healing, the control of wound infection is more important [18]. The aim of this study is to re-appraise the problem of limitation of wound dressing selection in the developing countries. We are still hoping to acquire newer agents for wound dressing, in the developing countries, we have made an effort to discuss some characteristics needed to make us choose wisely from the limited variety of dressing materials to meet the needs of our wounds for efficient wound care. This is with the aim of sensitizing the wound care practitioner on the use of the commonly little available products based on the needs of a different wound or even the same wound throughout its healing course.

Wound healing managements

Effective wound management depends on understanding a number of different factors such as the type of wound being treated, the healing process, patient conditions in terms of health (e. g. diabetes), environment and social setting, and the physical chemical properties of the available dressings [19]. It is important therefore, that different dressings be evaluated and tested in terms of their physical properties and clinical performance for a given type of wound and the stage of wound healing, before being considered for routine use.

Several factors apart from the choice of wound dressings need to be considered to ensure successful wound healing. In the case of chronic wounds, underlying factors such as disease, drug therapy and patient circumstance must all be reviewed and addressed before a particular wound dressing is applied. Table 1 [20] describes factors to be considered in the choice of wound dressings based on their performance characteristics (functions) [21-23]. In the past, traditional dressings (table 2) such as natural or synthetic bandages, cotton wool, lint and gauzes all with varying degrees of absorbency were used for the management of wounds. Their primary function was to keep the wound dry by allowing evaporation of wound exudates and preventing entry of harmful bacteria into the wound. Modern dressings are based on the concept of creating an optimum environment to allow epithelial cells to move unimpeded, for the treatment of wounds. Such optimum conditions include a moist environment around the wound, effective oxygen circulation to aid regenerating cells and tissues and a low bacterial load. Other factors which have contributed to the wide range of wound dressings include the different type of wound (e. g. acute, chronic, exuding and dry wounds, etc.) and the fact that no single dressing is suitable for the management of all wounds. In addition, the wound healing process has several different phases that cannot be targeted by any particular dressing.

The use of topical pharmaceutical agents in the form of solutions, creams, ointments and incorporated drugs i.e. active compounds and the dressings (novel polymer systems) play an active role in the wound healing process either directly or indirectly as cleansing or de briding agents for removing necrotic tissue, antimicrobials which prevent or treat infection or growth agents (factors) to aid tissue regeneration and also possess antiseptic and antibacterial actions. Some dressings such as gauze and saline are useful for the initials stages of wound healing for absorbing blood and exudates, cleansing and debridement. Other dressings provide a moist environment during the latter stages of wound healing, whilst some medicated dressings and biomaterials can take active part in all the stages of wound healing. In most cases, a combination of dressings is needed in order to achieve complete wound healing in a reasonable time. Wound healing formulations (dressings) and novel technologies developed to date focus on one or more of these aspects of the natural healing process [24] that are summarized briefly in table 3.

Most modern dressings are made from polymers which can serve as vehicles for the release and delivery of drugs to wound sites. The polymeric dressings employed for controlled drug delivery to wounds include hydrogels such as poly (lactide-co-glycolide) [25] poly (vinyl pyrrolidone) [26], poly (vinyl alcohol) [23] and poly (hydroxyalkylmethacrylates) [37-39] polyurethane-foam [40-44], hydrocolloid [45] and alginate dressings [46-49]. Other polymeric dressings reported for drug delivery to wounds comprise novel formulations prepared from polymeric biomaterials such as hyaluronic acid [50, 51], collagen [52, 53] and chitosan [54-57]. Synthetic polymers employed as swellable dressings for controlled drug delivery include silicone gel sheets [58], lactic acid [59]. Some of these novel polymeric dressings for drug delivery exist as patents [60-65]. Composite dressings comprising both synthetic and naturally occurring polymers have also been reported for controlled drug delivery to wound sites [66, 67]. Sustained release tissue engineered polymeric scaffolds for controlled delivery of growth factors and genetic material to wound sites has also been reported [68, 69]. The modern dressings for drug delivery to wounds may be applied in the form of gels, films and foams whilst the novel polymeric dressings produced in the form of films and porous sponges such as freeze-dried wafers or discs [70-77] or as tissue engineered polymeric scaffolds [70, 78](table 4) (fig. 1).

Bioengineered skin substitutes, both biosynthetic skin substitutes and cultured autologous engineered skin, are available to provide temporary or permanent coverage, with the advantages of availability in large quantities and negligible risk of infection or immunologic issues. With advances in burn resuscitation and critical care management, more patients with significant body surface area burns are surviving, leading to the issue of coverage of large wounds. Autograft is currently the preferred option, but in many instances there is an insufficient amount of tissue available for grafting, or the patient’s condition precludes the use of autograft. Allografts and xenografts can provide a temporary coverage option, but they come with issues regarding rejection, and possible disease transfer, availability, as well as cultural and ethical considerations. Biobrane is a temporary dressing composed of knitted nylon mesh bonded to a thin silicone membrane and coated with porcine polypeptides [79]. It is used in clean superficial and middermal depth burns or as coverage for donor sites in split-thickness skin grafting. Trans Cyte is a biosynthetic dressing of a semipermeable silicone membrane on a nylon mesh coated with porcine collagen and newborn human fibroblast cells [79]. It is used as a dressing in superficial burns that do not require skin grafting, or as a temporary cover for excised burns prior to grafting. Dermagraft contains neonatal fibroblasts on a bioabsorbable polyglactin mesh. The fibroblasts produce dermal collagen, glycosaminoglycans, growth factors, and fibronectin to support wound healing [80]. It is a temporary or permanent cover used for excised burn wounds as well as venous ulcers and pressure ulcers [79]. Results show it to be comparable to allograft for wound infection, healing time, exudates, and graft take, with higher patient satisfaction [81, 82]. Apligraf is composed of an epidermal layer of allogeneic neonatal keratinocytes and fibroblasts from neonatal foreskin on bilayered type I bovine collagen [79, 83] that is used as an adjunct covering to autograft, providing accelerated healing times [80]. It is also used alone in chronic wound ulcers, showing increased healing times when compared to controls [84]. Integra is a semibiologic bilayered dressing composed of a matrix of type I bovine collagen, chondroitin-6-sulfate, a glycosaminoglycan from shark cartilage, under a temporary silicone epidermal sheet [79, 85]. The pore size (70–200 μm) is designed to allow migration of the patient’s own endothelial cells and fibroblasts. As the wound heals, the silicone sheet is removed and a thin autograft is grafted onto the neodermis to complete the wound coverage.

Recently, the method of delivering growth factors from outside the body using a drug delivery system is being researched for the treatment of chronic wounds [86]. Growth factors stimulate mainly fibroblasts and keratinocytes via transmembrane glycoproteins [87]. The development of modern wound dressings, which mimic exactly the missing matrix, is the most comprehensible approach for the treatment of non-healing wounds. For the aforementioned reasons, nanofibers can be used as efficient natural extracellular matrix (ECM) analogues. After the application onto the wound, cells will take the latter as if synthesized by themselves and consequently oriented chemotaxis, adhesion, differentiation and cell growth will be stimulated as well as the formation and deposition of a provisional matrix and re-epithelialization [88-90].

Future strategies and approaches

The goal of wound healing management need not always be a more rapid healing, but rather can also encompass a reduction in pain or improved quality of life. With the development of various results, including the complete healing, little pain when attaching and detaching the wound dressing, etc, there will no doubt be significant crossover in wound dressing that leads to better, safer, and more integrated original tissue. The primary wound treatment method has been changing from the dry method in the 1900s and the wet method in the 1970s to the drug delivery system (DDS) method today. In the past, the dry dressings were used where the wound was disinfected and a crust was formed which would come off when the wound was healed. Nowadays, the wet dressings are used frequently; these dressings maintain the wetness of the wound site, accelerate the recovery speed, minimize scarring, and do not cause the formation of a crust [91]. In addition, the wet dressing has a significant amount of contact with the wound site so that it results in little secondary damage and prevents pathogens and foreign substances from entering the wound.

As technology and engineering processes become increasingly sophisticated, it seems ideal to have composite dressings which combine the different characteristics of current technologies. This will aid in targeting the many aspects of the complex wound healing process, to ensure effective, complete wound healing and shorter healing times for chronic wounds (and other difficult to heal wounds). It may also be expedient to employ individualized therapeutic approaches for treating specific wound types and individuals using emerging tissue engineering technologies. Such advanced approaches can help treat chronic wounds in a clinically efficient manner. One can only anticipate that further development of biocompatible scaffolds will result in a range of sophisticated dressings that will be capable of facilitating migration and proliferation through the controlled release of cytokines and growth factors, in response to biomarkers present in the wound environment, while impeding infection and relieving pain. Each wound arises from a unique cause, be it a particular trauma or underlying condition on a unique patient. This requires a range of dressings to ensure optimal healing conditions for all wounds and, ultimately, a suite of sophisticated dressings that possess all of the features of an ‘ideal dressing’ while catering to the individual.

More recently the hyperbaric oxygen therapy in diabetics with chronic foot ulcers (HODFU) study was completed [92, 93]. This suggests that in addition to immediate assistance in healing, hyperbaric oxygen also has a role in long-term wound improvement, perhaps as the full effects of neovascularization are realized. Negative pressure wound devices are relatively new in wound care treatment, and their indications are continually expanding to encompass aspects of wound management that previously had very few options. With the advent of biosynthetics and tissue engineering, skin substitutes are being created that not only provide novel effective temporary coverage of wounds, but are also changing the paradigm of wound management. By supporting the wound with growth factors and biologic substances, we can help augment or modulate the wound healing process itself. There may be many unexplored polymeric dressings with idealised properties required for the effective and sustained delivery of therapeutic agents to chronic wounds and it is hoped that this article can provide a key to this knowledge.

Table 1: Desirable characteristics and clinical significance for wound healing

Desirable characteristics

Clinical significance for wound healing

Debridement (wound cleansing)

Enhances migration of leucocytes into the wound bed and supports the accumulation of enzymes. Necrotic tissue, foreign bodies and particles prolong the inflammatory phase and serve as a medium for bacterial growth

Provide or maintain a moist

wound environment

Prevents desiccation and cell death, enhances epidermal migration, promotes angiogenesis and connective tissue synthesis and supports autolysis by rehydration of desiccated tissue

Absorption. Removal of blood and excess exudate

In chronic wounds, there is excess exudate containing tissue degrading enzymes that block the proliferation and activity of cell and break down extracellular matrix materials and growth factors, thus delaying wound healing.

Gaseous exchange (water vapour and air)

Permeability to water vapour controls the management of exudate. Low tissue oxygen levels stimulate angiogenesis. Raised tissue oxygen stimulates epithelialisation and fibroblasts

Prevent infection: Protect the wound from bacterial invasion

Infection prolongs the inflammatory phase and delays collagen synthesis, inhibits epidermal migration and induces additional tissue damage. Infected wounds can give an unpleasant odour.

Provision of thermal insulation

Normal tissue temperature improves the blood flow to the wound bed and enhances epidermal migration

Low adherence. Protects the wound from trauma

Adherent dressings may be painful and difficult to remove and cause further tissue damage

Cost effective low frequency of

dressing change

Dressing comparisons based on treatment costs rather than unit or pack costs should be made (cost-benefit-ratio). Although many dressings are more expensive than traditional materials, the more rapid response to treatment may save considerably on total cost


Table 2: Traditional wound dressings in the world market

Dressing material

Brand name

Manufacturer

Paraffin gauze dressing containing

0.5% chlorhexidine acetate

Bactigras

Smith & Nephew

Paraffin gauze dressing

Jelonet

Smith & Nephew

Petrolatum gauze

Xeroform

Chesebrough-Pond’s Inc.

Petrolatum gauze containing 3% bismuth tribromophenate

Xeroform

Chesebrough-Pond’s Inc.

Scarlet Red dressing

Scarlet Red

Chesebrough-Pond’s Inc.

Sterile hydrogel dressing

2nd skin®

Spenco

Highly absorbent cotton wool pad

Gamgee® pad

3M

Highly absorbent rayon/cellulose blend sandwiched with a layer of antishear high density polyethylene

Exu Dry Dressing

Smith & Nephew

Absorbent cotton pad

Telfa "Ouchless"

Nonadherent Dressings

Kendall (Covidien)

Source: Sezer AD et.al. 2011


Table 3: Advances in wound healing managements

S. No.

Dressings

Managements

1

Protective dressings

Gauze

Inexpensive; Traumatic removal, lateral bacterial migration.

Bandage

Readily available; Cheap; accessible; Efficacy to retain and absorb exudates varies; need to be changed regularly to prevent maceration.

Impregnated gauze

Nonadherent; Preserves moisture; May not prevent maceration.

2

Honey dressing

Antimicrobial, antifungal, deodorizing, anti-inflammatory, maintains moist environment; As a topical treatment, it rapidly dilutes and requires frequent dressings to maintain efficacy.

3

Antimicrobial dressings

Antibacterial ointments

Needs to reapply often to maintain moisture

Iodine based

Absorbent; Antiseptic, only small amounts of free iodine released into wound site; not for use with thyroid; through cytotoxic action against fibroblasts, keratinocytes and leukocytes; only suitable for short-term use.

Silver based

Antibacterial action well established; broad spectrum; Possible systemic toxicity currently being investigated; Effectiveness varies between products.

4

Autolytic debridement

Films

Occlusive; allows exchange of gasses

Hydrocolloids

Provides a moist, hypoxic wound environment; Not for exudative or infected wounds

Hydrogels

Can provide moisture to dry wounds as well as absorb excess exudates depending; Atraumatic when used correctly; Facilitates autolysis of necrotic tissue, and does not support bacterial growth.

5

Chemical debridement

Papain/urea

Availability issues in US

Collagenase

Selective debridement

6

Absorbent dressings

Foams

Can be cut to any shape, thermally insulating, provides moist interface, absorbs excess exudate, impregnable; Absorbs moderate exudates; Not suitable for dry wounds.

Hydrogels

Rehydrates to soften dry wounds; Only suitable for low exuding wounds or dry wounds. Can cause maceration in heavily exuding wounds, can shift from dry to wet gangrene in exuding ischaemic ulcers.; Absorbs minimal exudate

Hydrofibers

Absorbs heavy exudate

Alginates

Absorbs heavy exudates; They are unsuitable for dry wounds or dry hardened necrotic tissue.

7

Soft Silicone

Prevents maceration of the surrounding tissue, atraumatic removal with nonadherence to the wound site, suitable for wide range of wound types, can be used for difficult wound sites, can be left for up to 10 days, can be impregnated with silver. Used in conjunction with secondary absorbent dressing, requires contact with the wound site.

8

Scaffolds

 

Scaffold–

natural material

(Alloderm)

Biocompatible, degradable, and is low in antigenicity; Collagen may enable the transmission of infectious agents and thus requires vigorous disinfection protocols

 

Scaffold–

Synthetic material

(Integra)

Variety of methods of construction, electrospun scaffolds stimulate cellular adhesion. Polylactides degrade to lactic acid ensuring limited host immune response. Localised production of lactic acid may affect the efficacy of some proteins in the local environment.

Source: Murphy PS et. al.2012; Daunton C et. al.2012


Table 4: Novel drug delivery approaches for wound healing managements

S. No.

Company/Products

Descriptions

1

Activa Healthcare

Flivasorb®

Absorbent Dressings

These dressings are indicated for highly exuding wounds and/or as a secondary dressing. *QIPP TIP-Where possible use dressing pads before using super absorbent dressings.

Molnlycke

Mextra superabsorbent

2

ConvaTec

Carboflex®

Activated Charcoal Dressings

Indications for use include malodorous exuding wounds such as fungating and/or malignant wounds and also infected wounds. *QIPP TIP-Charcoal becomes rapidly deactivated once it becomes wet.

3

ConvaTec

Kaltostat®

Kaltostat® Rope

Alginate Dressings

Suitable for a wide range of wound types including cavities, granulating and, sloughy wounds with moderate-to-high levels of exudate. Kaltostat is especially useful for haemostasis in bleeding wounds. Caution is needed as blood clots can adhere to the wound surface. *QIPP TIP-Alginate dressing needs to be cut approximately to the size of the wound as the exudate will transfer laterally.

4

Smith and Nephew

Iodoflex®

Anti-Microbial-Cadexomer Iodine Dressings

Cadexomer iodine is recommended for infected wounds. It should not be used in children, pregnant or lactating women or people with renal impairment or thyroid disorders or those receiving Lithium treatment. Maximum single 50g and 150g weekly application. *QIPP TIP–If wound not improving to treatment after 4 weeks treatment refer to tissue viability service

5

Advancis

Activon Tulle®

Algivon®

Actilite®

Activon® Tube

Anti-Microbial-Honey Dressings

Beneficial in the management of chronic wounds, including the reduction of odour, anti-inflammatory activity and the stimulation of healing. Should not be used on patients with allergy to bee stings or bee products or in patients with extreme sensitivity to honey. *QIPP TIP–Monitor blood glucose for patients who have diabetes.

6

Activa Healthcare

Suprasorb® X+PHMB

Rope

Anti-Microbial-PHMB Dressings

This dressing is an antimicrobial hydrobalance wound dressing. It is suitable for use in a wide variety of wounds such as leg ulcers, pressure ulcer etc. *QIPP TIP–It is used to reduce the wound bioburden. If no improvement after 4 weeks use refer to tissue viability service

7

Smith and Nephew

Acticoat®

Acticoat® 7

Acticoat® Absorbent

Acticoat® Flex 3

Acticoat® Flex 7

Anti-Microbial Dressings–Silver Dressings

Should be reviewed regularly: weekly and long term use should be avoided. Where there are large amounts of exudate present an absorbent silver dressing should be used. Not compatible with saline. *QIPP TIP-Not recommended for routine use in chronic venous leg ulcers, uncomplicated ulcers, acute wounds. Dressing should be changed every 3-7 days. If wound does not improve refer to tissue viability service

8

3M Health Care

Tegaderm®

Film Dressings

Suitable for shallow wounds and can be used as a secondary dressing, they protects newly epithelialising wounds from trauma. Additionally they can be used to protect skin from exposure to friction. Care needs to be taken while removing dressings and many have a specific method to break the adhesive bond to ensure a non-traumatic removal.

Smith and Nephew

IV 3000 Adhesive IV Film dressing Peripheral lines

PICC Line

For Central Lines

9

Smith and Nephew

Allevyn® Adhesive

Sacral

Allevyn® Gentle Border

Heel

Allevyn® Gentle Border Lite

Allevyn® Gentle

Allevyn® Non Adhesive

Foam Dressings

Foams can be used on a variety of wounds including pressure ulcers, leg ulcers, burns, surgical wounds, etc. as a primary or secondary dressing. They are available in adhesive bordered format, although some are non-bordered and some are more suitable for delicate or problematic skin. Foams are best suited for exuding wounds and are not recommended for dry superficial wounds. *QIPP TIP-Consider the size of the wound when selecting shaped dressings such as heel or sacral as it may be better to use a 10 cm X 10 cm dressing if the wound is small

Coloplast

Biatain® Adhesive

Biatain® Non Adhesive

Biatain® Silicone

10

Coloplast

Comfeel Plus Ulcer

Sacral

Contour

Hydrocolloids

Comfeel is often used to debride necrotic tissue. Duodermis used to protect fragile skin or as secondary dressing. Can be used on a variety of wounds including pressure ulcers, leg ulcers, surgical wounds and minor burns. They can be used in granulating wounds and they can aid in the rehydration and debridement of dry, sloughy and necrotic wounds. *QIPP TIP-Avoid bordered hydrocolloids as these do not always adhere and may require more frequent changing due to increase exudate levels.

ConvaTec

DuoDERM® Extra Thin

11

ConvaTec

Aquacel® Extra

Aquacel®

Aquacel® Foam

Adhesive

Aquacel® Foam non

adhesive

Hydrofiber® Technology

Suitable for use in a wide variety of wound types including leg ulcers and pressure ulcers with moderate to high levels of exudate. The dressing absorbs and locks away large amounts of exudate and reduces the likelihood of peri-lesion maceration or excoriation. *QIPP TIP-Please ensure that you request Aquacel and not Aquacel AG as this contains silver and is not on formulary

12

Systagenix Wound Management

Nu-Gel®

Hydrogel

These can be used on dry and sloughy wounds and are good at hydrating dry wounds by providing a moist wound environment. They have been shown to reduce pain.*QIPP Tip-Hydrogels possess a high water content and should not be used in highly exuding wounds.

Smith and Nephew

Intrasite®

Intrasite® Conformable

13

Paul Hartman Ltd

Atrauman

Wound Contact Layer

Primary dressings used for low exuding, granulating wounds. Suitable for use under compression bandaging systems. Adaptic Touch can be used on superficial burns to prevent trauma to the wound bed and make dressing changes less painful

Systagenix Wound Management

Adaptic Touch

14

Activa Health Care

Activa Leg Ulcer

Hosiery Kit

Leg Ulcer Hosiery Kits

Hosiery kits allow for cost effective treatment of small venous leg ulcers. This allows patients to self-manage where possible. Kits are less bulky than bandages, which may improve comfort and mobility

Medi UK

Mediven Ulcer Kit

Standard

Mediven Ulcer Kit Petite

15

Smith & Nephew

Sheet

Strips

Heel

Sacrum/ankle wrap

Aderma Dermal Pads

Polymer gel-shaped pad that redistributes pressure while protecting and padding bony prominences used for pressure ulcer prevention. *QIPP TIP–These pads are washable and reusable.

16

Activa Health Care

Debrisoft®

Active Debridement Pad

A soft pad of monofilament polyester fibres intended as a rapid, highly effective and safe debridement method for the removal of loose soft slough in superficial wounds and the surrounding skin. *QIPP TIP–Consider using in shallow pressure ulcers with light covering of soft slough prior to pressure ulcer grading.

17

Smith & Nephew

Renasys® G with Soft Port Gauze Dressing Kit

Renasys® F with Soft Port Foam Dressing Kit

Renasys® Go Canister Kit

Renasys® Y Connector

Negative Pressure Wound Therapy (NPWT)

This is used for the management of large wounds such as cavity wounds with high exudate. Equipment should be requested from the Integrated Community Equipment Store. Please contact the Tissue Viability Service for support and advice.

18

3M Health Care

Tegaderm® Matrix

Protease Modulators

Chronic wound healing is characterised by a protracted inflammatory phase as a result of altered biochemistry where elevated levels of proteases are found. The consequences of this distorted biochemical profile is that tissue degrading enzymes matrix metalloproteases (MMPs) interfere with protein synthesis and denature growth factors. These dressings are designed to interact with the wound and modulate protease activity.

 

Systagenix Wound Management

Promogram®

Promogram® Prisma

19

Biomond

BioBag®

Larvae Therapy

A Biosurgical treatment for the debridement of wounds. The larvae are sealed within a dressing which is a finely woven net pouch containing a small piece, or pieces of foam, which aid the growth of the larvae. The larvae remain sealed within the dressing throughout the treatment.

20

Smith & Nephew

PICO®

PICO

Indicated for a range of wound types including chronic wounds, incision sites, acute wounds, traumatic wounds, sub-acute and dehisced wounds, partial-thickness burns, ulcers (such as diabetic or pressure), flaps and grafts, dermal substitutes.* QIPP TIP–Due to the large cost of these dressings. This treatment is only to be prescribed following assessment by The Tissue Viability Service.


ELFT Formulary Development 2014, Wound Dressing Formulary NHS foundation trust East London 2014, *QIPP TIP-Quality Innovation, Productivity and Prevention tips

Fig. 1(a): A typical hydrocolloid dressing, (TegasorbTM). It combines moisture vapour permeability with absorbency, conformability and its transparency allows for wound observation

Source: Boateng JS. et al. 2007

Fig. 1(b): Polymeric hydrogel sheet for wound dressing. It does not need a secondary dressing and due to their flexible nature, can be cut to fit around the wound

Source: Boateng JS. et al. 2007

Fig. 1(c): Lyofoam® Max is designed for the management of moderately to highly exuding wounds. Its high absorbency and fluid handling capacity combined with the reduced risk of maceration

Source:http://www.klinemedicalsupply.com/Wound-Care

Fig. 1(d):Application of Kalypto forefoot wound dressing.

Source: http://www.diamondrx.com

Fig. 1(e): Pictured here are biosynthetic wound dressing gloves.

Source: Wounds 15(1):4-9, 2003. © 2003 Health Management Publications, Inc

Fig. 1(f): Management of superficial partial thickness burns with Biobrane (15/3 denier nylon fibers) Source: Greenwood JE. et al. 2009

Fig. 1(g):A transdermal adhesive is suitable for use in drug-delivery and combination devices. Offered as part of a company’s drug-delivery silicone family, DDR-1370 is a traditional pressure-sensitive adhesive (PSA), while DDR-4355 is a strong-tack silicone gel.Can be used in wound-care applications for dispensing pharmaceutical ingredients such as antibiotics, anti-inflammatory drugs, or antimicrobials. Source: www.nusil.com

Fig. 1: Medicated dressings for drug delivery in wound healing managements


CONCLUSION

This article has considered many classes of wound dressings including topical pharmaceutical agents, traditional wound dressings and modern dressings such as hydrocolloids, alginates, hydrogels, polyurethane film and foam and novel biomaterials such as collagen, chitosan and hyaluronic acid used directly or as tissue engineered matrices for skin replacement. Polymeric dressings designed as vehicles to deliver therapeutic agents directly to the surface of wounds have also been discussed. These include alginates, chitosan, pectin and hyaluronic acid as polymers of natural origin; collagen sponges and other hydrogel materials; artificial skin grafts and tissue engineered products. The mechanism(s) for the controlled delivery of drugs from polymeric dressings were also considered and the requirement for the development of novel dressings with improved residence on the wound site (prolonged delivery) was also solicited.

Effective dressings should have properties and delivery characteristics that are optimised for specific wound types with minimum or no inconvenience to the patient and at reasonable cost. To achieve such objectives, manipulation of the physical characteristics of the identified systems is necessary. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. Faced with the prospect of increased prevalence of antibiotic-resistant pathogens, and the diminished effectiveness of current therapies, careful consideration of treatment options is now important. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing. This article extends the information and hopes to give insight into past, present and future treatment strategies and approaches for wound healing management.

ACKNOWLEDGEMENT

I gratefully acknowledge the encouragement and guidance given to me by Dr R. S. Pawar, Associate Professor, VNS group of institutions, Bhopal MP and grateful to Indian council of medical research for providing financial support as ICMR-SRF.

CONFLICT OF INTERESTS

Declared None

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About this article

Title

NOVEL DRUG DELIVERY STRATEGIES AND APPROACHES FOR WOUND HEALING MANAGEMENTS

Date

01-04-2015

Additional Links

Manuscript Submission

Journal

Journal of Critical Reviews
Vol 2, Issue 2, 2015 Page: 12-20

Online ISSN

2394-5125

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Authors & Affiliations

Fedelic Ashish Toppo
Pharmacognosy and Phytochemistry Laboratory, Faculty of Pharmacy, VNS Group of Institutions, Neelbud, Bhopal, Madhya Pradesh, India 462044

Rajesh Singh Pawar


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