In vivo wound healing performance of drug loaded electrospun composite nanofibers transdermal patch

Acute injuries or wound is required the fast delivery of drug to control infections without any side effect. In this direction in the present investigation, antibiotic ciprofloxacin loaded hydrophilic biodegradable poly vinyl alcohol (PVA) and sodium alginate (NaAlg) electrospun composite nanofiber based transdermal patch was developed for local delivery of antibiotic drug. The antibiotic drug ciprofloxacin was loaded in it by active loading. The drug entrapped in the composite nanofibers was confirmed by the scanning electron microscopy and swelling behavior. The in vivo studies were carried on male rabbits by using the drug loaded and unloaded composite nanofibers transdermal patch and marketed one. It is observed that, in vitro activity provides a sustained and controlled release pattern of the drug from transdermal patch. The mechanism of drug release was also studied using different models. The nanofiber transdermal patch follows the Higuchi and Korsmeyer–Peppas model for drug release. The in vivo studies demonstrate that, wound healing takes place in less time as compared drug unloaded patch. Hydroxyproline produced in wound bed with time shows that it content is maximum in case drug loaded PAV-NaAlg patch. This demonstrates that wound healing rate is higher in case drug loaded PVA-NaAlg transdermal patch.     

Formulation and evaluation of Ocimum basilicum-based emulgel for wound healing using animal model

The main aim of the topically applied drugs is to provide local drug contact to the skin and minimize general absorption of drugs. Ocimum basilicum (OB) is popular for folk medicines, having official acceptance in many countries. The aim of this study was to formulate and evaluate the efficacy of topical application of OB-based emulgel on wound healing in animal model. The prepared formulations (OB emulgel) were assessed for FTIR analysis, stability studies, physical appearance, rheological behavior, spreadability, patch/sensitivity test and in vitro drug release. The in vivo wound healing effect was evaluated and compared with commercially available Silver Sulfadiazine cream Quench® in wound-induced rabbits by macroscopic and histopathological evidence. The OB extract/drug was compatible with the selected polymer and other excipients and indicated the suitability of the polymers/excipients for preparation of topical emulgel. The formulated OB emulgel exhibited good physical properties. The release profile of emulgel was satisfactory and released 81.71 ± 1.7% of the drug in 250 min. In vivo wound healing studies showed that OB emulgel exhibited the highest percent wound contraction similar to the commercial product (p > 0.05). This activity was statistically significant (p < 0.05) in comparison to control. Histopathological assessment showed marked improvement in the skin histological architecture after 16 days of OB emulgel treatment. In conclusion, the data demonstrated here signify the prospective of 5% OB emulgel as an innovative therapeutic approach in wound healing.     

An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery

In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.     

Antiallodynic and Antihyperalgesic Activities of Fentanyl-Loaded Dermal Clay Dressings in Rat Model of Second-Degree Burn Injury

Second-degree burn injury is the most common type of burn injury, which usually takes 2-3 weeks for complete healing. However, such patients suffer with intense pain associated with development of hyperalgesia and allodynia. Here, we prepare a silver clay patch using montmorillonite clay, betaine, and silver nitrate. Later, the silver clay patches were loaded with fentanyl. Furthermore, the patches were fabricated into burn wound dressings. The dressings were first subjected to ex vivo skin penetration studies and were later evaluated for thermal hyperalgesia and mechanical allodynia using second-degree burn injury rodent model. Our results show that application of fentanyl-loaded dermal clay (FLDC) dressings for 3 h showed significant increase of paw withdrawal latency (p <0.001) against hyperalgesia starting from 30 min after removal of patch to up to 6 h. Similarly, the FLDC dressings also potentiated the paw withdrawal threshold for up to 4 h after application (p <0.001). From these studies, we can conclude that FLDC dressings are ideal topical formulations for better management of pain in second-degree burns.     

Formulation and characterization of propolis and tea tree oil nanoemulsion loaded with clindamycin hydrochloride for wound healing: In-vitro and in-vivo wound healing assessment

This study aimed to develop propolis and tea tree oil nanoemulsion loaded with clindamycin hydrochloride to heal wound effectively. Nanoemulsion formulae were prepared and characterized by droplet size analysis, zeta potential, viscosity, ex-vivo permeation, and skin deposition. The optimal formula was evaluated in terms of morphology, cytotoxicity, and in-vitro wound healing assay. Also, the efficacy of the optimal formula was evaluated by in-vivo wound healing and histopathological studies. The optimal formula (F3) was composed of 9% tea tree oil and 0.4% propolis extracts with mean droplet size 19.42 ± 1.7 nm, zeta potential value −24.5 ± 0.2 mV, and viscosity 69.4 ± 1.8 mP. Furthermore, the optimal formula showed the highest skin deposition value 550.00 ± 4.9 µg/cm² compared to other formulae. The TEM micrograph of the optimal formula showed that the nanoemulsion droplet has an almost spherical shape. Also, the optimal formula did not show noticeable toxicity to the human skin fibroblast cells. The in-vitro and in-vivo wound healing assay showed unexpected results that the un-loaded drug nanoemulsion formula had a comparable wound healing efficacy to the drug-loaded nanoemulsion formula. These results were confirmed with histopathological studies. Our results showed that the propolis and tea tree oil nanoemulsion, whether loaded or unloaded with an antibiotic, is an efficient local therapy for wound healing.     

Alginate and alginate composites for biomedical applications

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.     

In vitro and in vivo evaluation of an intraocular implant for glaucoma treatment

This study investigated critical physicochemical attributes of low (LV), medium (MV) and high molecular weight (HV) sodium carboxymethylcellulose (SCMC) scaffolds in partial thickness wound healing. SCMC scaffolds were prepared by solvent-evaporation technique. Their in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution, and in vivo wound healing profiles were determined. Inferring from rat wound size, re-epithelialization and histological profiles, wound healing progressed with HV scaffold>LV-MV scaffold>control with no scaffold. The transepidermal water loss (TEWL) from wound of rats treated by control>HV scaffold>LV-MV scaffold. HV scaffold had the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low moisture affinity characteristics. The HV scaffold can protect moisture loss without its excessive accumulation at wound bed which hindered re-epithelialization process. Regulation of transepidermal water movement and wound healing by scaffolds was governed by SCMC molecular weight instead of its carboxymethyl substitution degree or matrix pore size distribution, with large molecular weight HV preferred over lower molecular weight samples.     

Wound healing evaluation of sodium fucidate-loaded polyvinylalcohol/sodium carboxymethylcellulose-based wound dressing

The cross-linked hydrogel films containing sodium fucidate were previously reported to be prepared polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method and their physicochemical property was investigated. For the development of novel sodium fucidate-loaded wound dressing, here its in vivo wound healing test and histopathology were performed compared with the conventional ointment product. In wound healing test, the sodium fucidate-loaded composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug showed faster healing of the wound made in rat dorsum than the hydrogel without drug, indicating the potential healing effect of sodium fucidate. Furthermore, from the histological examination, the healing effect of sodium fucidate-loaded hydrogel was greater than that of the conventional ointment product and hydrogel without drug, since it might gave an adequate level of moisture and build up the exudates on the wound area. Thus, the sodium fucidate-loaded wound dressing composed of 5% PVA, 1.125% Na-CMC and 0.2% drug is a potential wound dressing with excellent wound healing.     

Local anesthetic lidocaine-encapsulated polymyxin–chitosan nanoparticles delivery for wound healing: in vitro and in vivo tissue regeneration

In relieving local pains, lidocaine, one of ester-type local anesthetics, has been used. To develop the lidocaine membranes of enhanced local anesthetic effects, we have designed to establish the composition of wound dressings based on lidocaine chloride (LCH) (anesthetic drug)-loaded chitosan (CS)/polymyxin B sulfate (PMB). The LCH membranes (LCH-CS/PMB) was fabricated by the LCH oxide solutions within the CS/PMB matrix. The influences of different experimental limitations on CS/PMB membrane formations were examined. The double membrane particle sizes were evaluated by scanning electron microscopy (HR-SEM). Additionally, antibacterial efficacy was developed for gram-positive and negative microorganisms. Moreover, we examined in vivo healing of skin wounds formed in mouse models over 16 days. In contrast to the untreated wounds, rapid healing was perceived in the LCH-CS/PMB-treated wound with less damaging. These findings indicate that LCH-CS/PMB-based bandaging materials could be a potential innovative biomaterial for tissue repair and regeneration for wound healing applications in an animal model.     

Clinical Potential of a Silk Sericin-Releasing Bioactive Wound Dressing for the Treatment of Split-Thickness Skin Graft Donor Sites

Purpose

An ethyl alcohol-precipitated silk sericin/PVA scaffold that controlled the release of silk sericin was previously developed and applied for the treatment of full-thickness wounds in rats and demonstrated efficient healing. In this study, we aimed to further evaluate the clinical potential of this scaffold, hereafter called “silk sericin-releasing wound dressing”, for the treatment of split-thickness skin graft donor sites by comparison with the clinically available wound dressing known as “Bactigras®”.

Methods

In vitro characterization and in vivo evaluation for safety of the wound dressings were performed. A clinical trial of the wound dressings was conducted according to standard protocols.

Results

The sericin released from the wound dressing was not toxic to HaCat human keratinocytes. A peel test indicated that the silk sericin-releasing wound dressing was less adhesive than Bactigras®, potentially reducing trauma and the risk of repeated injury upon removal. There was no evidence of skin irritation upon treatment with either wound dressing. When tested in patients with split-thickness skin graft donor sites, the wounds treated with the silk sericin-releasing wound dressing exhibited complete healing at 12?±?5.0 days, whereas those treated with Bactigras® were completely healed at 14?±?5.2 days (p?=?1.99?×?10^?4). In addition, treatment with the silk sericin-releasing wound dressing significantly reduced pain compared with Bactigras® particularly during the first 4 postoperative days (p?=?2.70?×?10^?5 on day 1).

Conclusion

We introduce this novel silk sericin-releasing wound dressing as an alternative treatment for split-thickness skin graft donor sites.