polimeric films.docx

8/10/2019 polimeric films.docx

http://slidepdf.com/reader/full/polimeric-filmsdocx 1/29

Biomed Res Int. 2014; 2014: 641590.Published online Jan 12, 2014. doi: 10.1155/2014/641590

PMCID: PMC3912760

Polymeric Films Loaded with Vitamin Eand A l o e v er a for Topical Application in theTreatment of Burn WoundsGabriela Garrastazu Pereira , 1 Sílvia Stanisçuaki Guterres , 1 AnnaGiulia Balducci , 2 Paolo Colombo , 2 and Fabio Sonvico 3 ,*

Author information ► Article notes ► Copyright and License information ►

AbstractGo to:

1. Introduction

Burns are among the most complex and harmful physicalinjuries to clinically evaluate and manage. In addition to pain and distress, a large burned area will leave the patientwith visible physical scars and invisible psychologicalsequelae [ 1, 2]. Concerning skin damage, the treatment of

burns is complex and painful and requires the use of severaldrugs administered separately or combined [ 3].

In human beings, the process of tissue reconstruction iscompleted with remarkable success, but it is unlikely thatthe body has exactly the same “tools” (raw materials andenvironment) to work as before, so there are limits

http://dx.doi.org/10.1155%2F2014%2F641590

http://dx.doi.org/10.1155%2F2014%2F641590

http://www.ncbi.nlm.nih.gov/pubmed/?term=Pereira%20GG%5Bauth%5D


http://www.ncbi.nlm.nih.gov/pubmed/?term=Guterres%20SS%5Bauth%5D



http://www.ncbi.nlm.nih.gov/pubmed/?term=Balducci%20AG%5Bauth%5D




http://www.ncbi.nlm.nih.gov/pubmed/?term=Colombo%20P%5Bauth%5D



http://www.ncbi.nlm.nih.gov/pubmed/?term=Sonvico%20F%5Bauth%5D



http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912760/














http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912760/#B1


















http://dx.doi.org/10.1155%2F2014%2F641590





being a potent moisturizing agent, it helps in the healing process of skin lesions and alleviates pain [ 15 – 17].

Another natural compound investigated in wound healing isvitamin E, a family of essential micronutrients with strongantioxidant activity composed of lipid-soluble tocopherolsand tocotrienols. Vitamin E may assist in wound healingthrough direct effects on tissue repair and regeneration[18, 19].

In relation to this, the objective of the present work has

been to develop and characterize a polymeric filmcontaining Aloe vera and vitamin E acetate with the aim of

providing an innovative system for burn wound treatment.The two polysaccharides selected to produce the film werehyaluronic acid and sodium alginate. Hyaluronic acid is anextracellular matrix component that forms a pericellularcoat on the surface of cells and has been shown to

contribute to the skin healing process [ 9, 20, 21]. Sodiumalginate, widely used in food and pharmaceuticalindustries, has been used in a number of wound treatments,for both acute or chronic wounds, because when it comesinto contact with the exudate or blood it forms a protectivefibrous gel, which is hydrophilic, hemostatic, and rich incalcium [ 22]. Polyvinyl alcohol was used as film formingagent and has been often used in combination with other

polymers for wound healing applications [ 23, 24].

Go to:

2. Material and Methods

































2.1. Materials

Aloe vera spray dried powder (200 : 1, aloe : mannitol) wasobtained from Brasquim (Porto Alegre, Brazil). Vitamin Eacetate (alpha tocopherol acetate) was purchased fromACEF (Fiorenzuola, Italy), hyaluronic acid solution with1% density 0.900 – 1.100g/cm 3was obtained from DEG (SãoPaulo, Brazil); polyvinyl alcohol (PVA) with molecularweight of 83,400Da was obtained from Nippon Gohsei(Osaka, Japan), sorbitol solution 70% was obtained fromACEF (Fiorenzuola, Italy), alginic acid (Satalgine) wasobtained from from Cargill (Saint-Germain-en-Laye,France) and poly(ethylene oxide) water soluble resin (PEO12 NF, 1000kDa) was obtained from Union Carbide(Milan, Italy). MilliQ ultrapure water (Millipore, Billerica,USA) was used for all experiments. All other chemicalswere of analytical grade.

2.2. A l o e v er a and Vitamin E Acetate Loaded FilmsPreparation

The composition of the dried films is reported in Table 1 . The films were prepared starting from two solutions.

Table 1 Percentage composition (% w/w) of vitamin E acetateand Aloe vera loaded polymeric films.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912760/table/tab1/

















Solution A. Alginate powder was added to 20mL of 1%w/w solution of hyaluronate and stirred until completedissolution. Aloe vera and vitamin E acetate were then

added.Solution B . In 10 mL of water and PEO, PVA and sorbitolwere dispersed under gentle heating until completesolubilization. The polymer solution obtained was allowedto stand for 4h, until all trapped air bubbles were removed.

Solutions A and B, prepared as described, were mixed

under magnetic stirring for 4 hours until reachinghomogeneity.

The polymeric films were produced by layering the polymeric viscous solution using a variable open castingknife (gap 2mm, BYK-Gardner GmbH, Geretsried,Germany) on a polyester translucent polyethylene laminatefilm (Scotchpak 1220 Backing, 3M Italia, Segrate, Italy)and by subsequent drying for 8h in an oven (55°C).

2.3. Physical Characterization of the Film

For each film produced, at least 3 disks of material (15 mmof diameter) were sampled by punching. Each disk wasaccurately weighed and its thickness was measured(Absolute Digimatic 547 – 401, Mitutoyo, Milan, Italy,sensitivity 0.001mm). Residual water content of eachformulation was determined using Karl-Fisher titration(TitroMatic KF 1S, Crison, Spain). Samples were analyzedin triplicate.



2.4. Vitamin E Acetate Assay

For each formulation, at least 3 disks (15 mm of diameter,surface area 176.7mm 2) were sampled. Each disk wasaccurately weighed and the sample then dissolved in 10mLof water: ethanol mixture (20 : 80 v/v) under sonication for2 h. The solution obtained was analyzed by HPLC in orderto determine the amount of vitamin E acetate contained inthe film. Vitamin E acetate analysis was performed byHPLC using the following experimental conditions: columnLiChrospher 100 RP18: 5 μ m, 250mm×3mm (Merck,Germany), mobile phase: methanol:isopropanol (50:50v/v), flow rate of 0.7 mL/min, and UV detection at 285 nm.Samples were filtered through 0.45 μ m (Ultracelregenerated cellulose, Microcon Filters, Millipore, USA)and were injected (20 μ L).

In these conditions, the retention time was about 6.6 min.

System suitability was checked according to the USP 24.The detector response was linear from 3 to 51 μ g/mL, witha limit of quantification of 0.42 μ g/mL, a limit of detectionof 0.13 μ g/mL, and r 2 0,9995.

The loading of vitamin E acetate in polymeric films wasexpressed as percentage by weight (% w/w) and as mg/cm 2.

In order to assess the influence of the tape (Scotch 845,3M, USA) and of the stratum corneum on the vitamin Eacetate assay, a vitamin recovery experiment was

performed. In brief, tape with or without stratumcorneum was extracted in methanol for 2 hours after adding





Suwon, Republic of Korea). Height images were displayedas 3D views. At least three regions of 10 × 10 μ m wereimaged for each film.

2.7. Mechanical Evaluation of Films

Films strips (10 × 70mm) were fixed between the twoclamps of an electronic dynamometer (Acquati, Milan,Italy) provided with a 5 kg load cell. The strips werestretched at the rate of 30mm/min; tensile strength (Ts b)and elongation at break ( ε b) were calculated as shown in ( 1)

and ( 2), respectively [ 25, 26]:Tsb=FbCs,

(1)

where Ts b (N/mm 2) is the tensile strength, F b is the breakingforce (N), and C s is the cross-sectional area of the sample(mm 2). Consider

εb=ΔLΔL0·100, (2)

where ε b is the elongation at break expressed as percentage,Δ L is the increase in length at the breaking point (mm),and L0 is the original length of the film (mm).

2.8. In Vi t r o Vitamin E Acetate Release Studies

A release assay of vitamin E acetate from films andcommercial cream containing the same quantity of vitaminE acetate was performed using modified Franz permeationcells with a synthetic membrane of regenerated cellulose

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912760/#EEq1










with 0.45 μ m pores (Millipore) to separate the donor andacceptor compartment. The in vitro release studies wereconducted on vertical diffusion Franz cells, having a

receptor compartment with a capacity of about 12.0mL anda diffusion area of 2.3cm 2 [27, 28]. The cellulosemembrane was kept in contact with a receptor solution

phosphate buffer pH 7.2 with 10% ethanol and 0.5% polysorbate 80 at a temperature of 37°C (±1°C) andconstantly stirred with a magnetic bar at 100rpm. Theacceptor medium was selected by determining thesaturation concentration of vitamin E acetate in differentcandidate receptor solutions, selecting the one that providedthe highest solubility, that is, 24.4 mg/mL.

For these studies films were used containing approximately630 μ g vitamin E acetate (approximately 2.0 cm 2 diameterdisks) or as reference product, 70mg of commercial cream

containing the same amount of drug. The material underinvestigation was placed in the donor compartment andhydrated with 500 μ L of phosphate buffer pH 7.2. The filmwas dipped in the buffer in order to allow drug release from

both surfaces and the formation of a gel in contact with themembrane.

At preestablished time intervals (each hour up to 12 hours),1 mL of the medium was removed and replaced by an equalvolume of preheated fresh receptor solution. Samples werefiltered through 0.45 μ m filters (RC, Millipore) before thedetermination by HPLC of their free vitamin E acetate









content according to the method described before. Theresults refer to the average of five experiments.

2.9. Tape Stripping

Five healthy volunteers (2 males and 3 females) participated in the study. All volunteers provided writtenconsent to participate in the study, having understood thedesign, objectives, and risks of the study. The participantswere aged between 26 and 37 years and had no history ofskin disease. Each participant was asked to refrain from

applying any topical medicaments to their left and rightflexor forearms at least 24h prior to the experiment. Thevolar forearm of each participant was wiped with water andsoap to remove any sebaceous lipids or contaminants on theskin surface. The participant extended both forearms over aworkbench with the volar forearm facing upwards.

Before applying each formulation, a circular region, 24mmin diameter, was defined on the treated area using a polyethylene adhesive template fixed to the arm. Threecircular regions were defined by each template in order tosimultaneously apply the film and the vitamin E containingcream. The third application site was left untreated toevaluate the vitamin E skin basal content.

The film formulation, cut into 24 mm diameter discs, was placed on the forearm skin surface and prewetted with afixed amount of 0.5mL water. After a few seconds of slight

pressure, the film adhered to the skin and was left in placefor 2 hours on the left forearm and for 4 hours on the right



forearm. A commercial cream containing 3.6% vitamin Eacetate was used as comparison. The vitamin E acetatecontaining semisolid formulation was applied at 15

mg/cm2

on a circular area of 24mm diameter. The removalof stratum corneum was performed with 20 adhesive tapestrips (Scotch 845, 3M, USA). Each strip was weighed

before and after the application on the skin in order toevaluate the amount of stratum corneum removed.

For each experiment, the tape strips were pooled in testtubes in sets of 4 subsequent strips, defining five depthsof stratum corneum penetration, from 1 superficial layer to5 deep layers and then extracted with 5ml of methanol.After one hour, the solution was filtered through 0.45 µmnylon filters and analyzed in HPLC.

2.10. Statistics

Data were evaluated by two-way analysis of variance(ANOVA) followed by Tukey's test (Kaleidagraph,Synergy Software, USA). The significance level appliedwas P < 0.05. The results of the experiments are expressedas the mean ± standard deviation.

Go to:

3. Results and Discussion3.1. Film Characterization

Three types of films were manufactured according to Table1. They differed for the amount of PVA and sodium












alginate. Thickness, weight, and residual water content ofthe polymeric films are shown in Table 2 . The films

presented thickness lower than 80 μ m and had a weight per

square centimeter close to 20 mg/cm2

. The amount ofvitamin E acetate in each film was about 3.5% by weight.They were flexible and resistant and could be easilyhandled, cut in the desired shape, and eventually deformedto adapt to the application site.

Table 2 Characterization and mechanical properties of vitamin Eand Aloe vera loaded polymeric films ( n = 6).

The films produced were shown to be completelysolubilized after 24 hours of immersion in distilled water.This is very important in the case of wound treatment, inview of the amount of wound exudates that are producedand which solubilize the film, causing the release of thefilm active substances.

Table 2 shows the characteristics and the mechanical

properties of the films. The mechanical properties requiredare flexibility and resistance to facilitate their use as potential wound-dressing materials. The strength andelasticity of the film were measured by the parameters:Ts b and ε b. The ε b of the film decreased with the increase of
















alginate content from F1 to F3. The stronger and lesselastic formulation was F3, with 2 : 1 ratio of alginate andhyaluronate. Formulation F1, with alginate/hyaluronate

ratio 1 : 1, showed a higher elongation at break and lowertensile strength. This behavior could be due to the higherwater content, provided by the hygroscopic contribution ofhyaluronate. The intermediate formulation F2 showed atensile strength equal to F1 and a percentage of ε bnotsignificantly different from F3. The films containing a 1.5 :1 alginate/hyaluronate ratio could be a compromise for theapplication to damaged skin, providing a relatively lowwater content, good resistance but, at the same time,flexibility.

According to the classification of Krochta and de Mulder-Johnston [ 29], the results indicate that the films produced inour study exhibit good elongation at break. In their study,

they reported that polymeric films of low-density polyethylene and polypropylene films showed an inverserelationship between tensile strength and elongation at

break. Similarly, in the present study, the formulation F3 presenting less elongation is characterized by greaterresistance, even if not significantly different from otherformulations.

A factor that must be controlled is the amount of plasticizers. The addition of the plasticizer reduces theintermolecular forces along the polymer chains, thusimproving the flexibility thereof, decreasing, however, thestress at break [ 30]. These interactions are needed to







prevent the films from becoming fragile and brittle,facilitating their handling and use although their use

promotes changes in the polymer structure. In the films

prepared, the increase in alginate content led to alower ε b and higher Ts b values despite a constant content ofthe plasticizer sorbitol. However, this could be significantlyrelated to reduction in residual water content. In fact, thewater molecules are generally regarded as the most natural

plasticizers of films based on hydrocolloids. Similar resultson the effect of moisture in tension and elongation at breakwere previously described for various hydrophilic films[31, 32]. A synergistic plasticizing effect of water andglycerol has been observed in carboxymethylcellulose filmswith consequent modification of mechanical properties and

polymer glass transition temperature [ 27].

3.2. Scanning Electronic Microscopy Analyses

Scanning electron microscopy was used to visualize thefilm surface (Figures 1(a) , 1(b) , and 1(c) ). Visualexamination of the SEM pictures indicated that the filmswere essentially smooth, with a slightly rougher surface forformulation F3. The films analyzed by SEM showed nochanges, heterogeneity, or component segregationdetectable on the surface or cross-section. The film F3

presented dark pits, suggesting the presence of holes thatarose during the drying process, possibly due to waterseparation, according to Dong and colleagues [ 22].






http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912760/figure/fig1/



















Figure 2 AFM images of polymeric films surface: (a) polymeric filmF1 (b) polymeric film F2, (c) polymeric film F3. Film

compositions are according to Table 1 . The drying of the film resulted in pores, which wereconfirmed by SEM and AFM imaging. These poresincrease the surface area, which could enhance theimmediate release of the substance from the polymersurface [ 28]. Moreover, the micrometric roughness of thesurface of the films can possibly allow them to offer alarger contact area to the healing tissue, which leads to amore efficient absorption of exudates, therefore enablingthe promotion of a more efficient repair of the burn wound[33, 34].

3.4. In Vi t r o Vitamin E Release Studies

A high elasticity and strength, together with a considerablethickness and a sufficient drug content per squarecentimeter, led to the selection of the film formulation F2for Franz cells and tape stripping experiments.

The study of the release profile provides essentialinformation regarding the structure and the molecular

behavior of the formulation, evidencing possibleinteractions between the drug and the polymer and theirinfluence on the rate and mechanism of the drug release.

The release of vitamin E acetate from the polymeric filmwas 30.1% of the total after 12 h. The patterns of release of


















vitamin E acetate from polymeric films are shown in Figure3. During the first hour of release, an immediate release ofthe vitamin occurred (around 13%) and after which the

vitamin release rate remained fairly constant (1.55% perhour).

Figure 3 Vitamin E release from polymeric film F2 (■) and cream(□) in phosphate buffer pH= 7.2 containing 10% ethanoland 0.5% polysorbate 80. Bars represent standardderivations of means of five determinations (mean andSD, ...

The amount of vitamin E acetate released after 12 hourswas much higher for the polymeric film than the release

measured in the case of the vitamin E acetate containingcream used for comparison. The amount of vitamin Eacetate diffused from the cream was lower than 1% of thetotal amount applied.

The cream formulation showed a very strong affinity forthe vitamin and hindering a partition with the water

acceptor phase. This observation can be related to theviscosity of the formulation and to the low water solubilityof the drug in the water media. In fact, discussing thesmaller release of vitamin E acetate from O/W emulsions,some authors attributed this fact to the formation of a















lamellar layer, formed by parallel surfactant bilayersseparated by layers of aqueous solvent and forming amono- or bidimensional network [ 35, 36]. This is

responsible for the viscosity of these formulations and iseventually able to entrap the vitamin, due to the presence ofmultiple hydrophilic layers, in which the vitamin is poorlysoluble, surrounding the oily phase in which vitamin E isdissolved.

Hydrophilic polymer films, like the formulation tested, provide a less important interaction with vitamin E acetatedispersed in them and a rapid water uptake, facilitating therelease in the aqueous environment. A rapid water uptakewith consequent immediate release, followed by theformation of a gel characterized by slower release, couldexplain the release pattern evidenced. The immediaterelease of the vitamin, shown at the beginning of the

experiment, may has been prompted by vitamin present onthe film surface. Subsequently, a gel layer is formed as aconsequence of water uptake of the film and hydration ofthe hydrophilic polymers contained in it, that is, alginateand especially hyaluronic acid. This behavior in vitaminrelease is also consistent with the experimental setup: thedonor compartment consists of a relatively small volume of

liquid, which is rapidly absorbed by the hydrophilic film.This is mimicking the exudate absorption that would occurin a real burn wound.

3.5. Tape Stripping









The in vivo performance of the film was evaluated usingthe tape stripping technique to measure the accumulation ofvitamin E acetate in the stratum corneum of intact skin

after the film application. Tape stripping has become aninvestigative technique used in both research of topical

bioavailability and bioequivalence, as proposed by FDA in1998 [ 37]. Even if interaction with intact skin is not goingto provide an evaluation of the efficacy of the formulationon burn wounds, it constitutes a good approach to comparethe performance of the polysaccharide film against atraditional semisolid topical formulation.The extraction of vitamin E acetate from the tapewith stratum corneum resulted in specific and efficientrecovery because no interference from skin componentswas present and the recovery was 101.65 ± 2.93%.

For each experiment, the tape strips were pooled in five

sets numbered from 1 to 5 with pool 1 corresponding to themore superficial layers and pool 5 to the more deep layersof stratum corneum . The cumulative amount of vitamin Eacetate recovered in the stratum corneum was alsocalculated (strips 1 – 20). The results obtained are reportedin Figure 4 . The comparison of the total recovery ofvitamin E acetate in the stratum corneum after theapplication of the polymeric film or of the cream showedthat the first was able to accumulate higher amounts ofvitamin E acetate in the stratum corneum (see Figure 4 ).This was confirmed for both application times, that is, 2and 4 hours. Furthermore, while the vitamin E acetate total











recovery is the same for the cream between 2 and 4 hours, amuch higher accumulation was registered for the film after4 hours. This result indicates different release patterns.

Figure 4 Cumulative vitamin E found per gram of skin from tapestrips for different formulations. Untreated skin has beenused as control (mean and SD, n = 5).

From Figure 5 , it is possible to appreciate that the vitaminE acetate contained in the films was able to permeate to thedeeper layers of stratum corneum and in greater quantitythan vitamin E acetate applied with the cream. It was alsoobserved that the films that remained for four hours on theforearm of the volunteers showed a greater amount of total

vitamin E acetate accumulated in those layers. The vitaminreleased by the film after 4 hours was able to reach thedeepest layers of the stratum corneum in a significantamount and probably efficiently attain the viable skinlayers. Vitamin E acetate content from the untreated skinwas found to be negligible compared to the vitamin

permeating from the formulations.

Figure 5


















healing process, acting in the deeper layers of the affectedarea. In particular, antioxidants, such as vitamin E, have

been shown to play a significant role in wound healing and

anti-inflammatory action. Preparations that increase freeradical scavengers in situ can offer protection from cellulardamage and facilitate the process of tissue repair [ 40].

Faster permeation through excised animal skin has beenevidenced for polymeric transdermal patches developed byPadula and colleagues [ 5]. Those patches, called Patch-non-Patch, are applied by wetting the skin and favoringfilm hydration and adhesion. The higher permeation ratesevidenced for a number of substances, compared tosemisolid formulations, have also been attributed to thecontribution of water to the increase in the constantdiffusion of substances in the film and in the stratumcorneum hydrated layers. A similar situation could be

hypothesized here to explain the much higher availability inthe stratum corneum of the vitamin E acetate through the polymeric film formulation. The hydrophilic componentsof the film provide adhesion in the presence of an aqueousmedium as exudates and the colloidal gel formed by thehydration of the polymer chains allow a better permeationof the poorly soluble and hydrophobic vitamin E [ 39].

Go to:

4. Conclusion

Bioadhesive polymeric films loaded with vitamin E acetateand Aloe vera were produced and tested on the intact skin












of healthy volunteers. The films showed mechanicalresistance and flexibility suitable for application in burnwounds. The release profile obtained from the film showed

a biphasic controlled release of vitamin E acetate for morethan 12 hours. The tape stripping on intact skin showedthat the polymeric film formulation facilitates a deeperaccumulation of the vitamin E acetate in the stratumcorneum when compared to a traditional semisolidformulation. The polymer film formulation containinghyaluronate and alginate appears to be a promisingapproach for the application of substances able to reducedamage and facilitate the healing process, like Aloevera extracts and the antioxidant vitamin E acetate.

Go to:

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

Go to:

References1. Boateng JS, Matthews KH, Stevens HNE, EcclestonGM. Wound healing dressings and drug delivery systems: a

review. Journal of PharmaceuticalSciences .2008;97(8):2892 – 2923. [PubMed ]2. Wolf SE, Sterling JP, Hunt JL, Arnoldo BD. The year in

burns 2010. Burns .2011;37(8):1275 – 1287. [ PubMed ]





http://www.ncbi.nlm.nih.gov/pubmed/17963217









3. Drago H, Marín GH, Sturla F, et al. The next generationof burns treatment: intelligent films and matrix, controlledenzymatic debridement, and adult stem

cells. Transplantation Proceedings . 2010;42(1):345 – 349. [ PubMed ]4. Kirker KR, Luo Y, Nielson JH, Shelby J, Prestwich GD.Glycosaminoglycan hydrogel films as bio-interactivedressings for woundhealing. Biomaterials . 2002;23(17):3661 – 3671. [ PubMed ]5. Padula C, Colombo G, Nicoli S, Catellani PL, MassimoG, Santi P. Bioadhesive film for the transdermal delivery oflidocaine: in vitro and in vivo behavior. Journal ofControlled Release . 2003;88(2):277 – 285. [ PubMed ]6. Sievens-Figueroa L, Bhakay A, Jerez-Rozo JI, et al.Preparation and characterization of hydroxypropyl methylcellulose films containing stable BCS Class II drugnanoparticles for pharmaceutical applications. International

Journal of Pharmaceutics .2012;423(2):496 – 508. [ PubMed ]7. Andrew B, Hari GG, Hales CA. Chemistry and Biologyof Hyaluronan . Oxford, UK: Elsevier Science; 2004. Ch18: Hyaluronan and scarring; pp. 367 – 394.8. Gong J, Chen M, Zheng Y, Wang S, Wang Y. Polymericmicelles drug delivery system in oncology. Journal ofControlled Release . 2012;159:312 – 323. [ PubMed ]9. Davidson JM, Nanney LB, Broadley KN, Whitsett JS,Aquino AM. Hyaluronate derivatives and their applicationto wound healing: preliminary observations. Clinical

Materials . 1991;8(1-2):171 – 177. [ PubMed ]















10. Goldberg SR, Diegelmann RF. Wound HealingPrimer. Surgical Clinics of North

America . 2010;90(6):1133 – 1146. [ PubMed ]

11. Jurjus A, Atiyeh BS, Abdallah IM, et al.Pharmacological modulation of wound healing inexperimental burns. Burns . 2007;33(7):892 – 907. [ PubMed ]12. Dantas MDM, Cavalcante DRR, Araújo FEN, et al.Improvement of dermal burn healing by combining sodiumalginate/chitosan- based films and low level lasertherapy. Journal of Photochemistry and Photobiology

B. 2011;105(1):51 – 59. [ PubMed ]13. Lademann J, Schanzer S, Richter H, et al. Formation ofa protection film on the human skin bymicroparticles. Laser Physics Letters . 2008;5(9):686 – 690.14. Reynolds T, Dweck AC. Aloe vera leaf gel: a reviewupdate. Journal of Ethnopharmacology . 1999;68(1 – 3):3 – 37. [ PubMed ]15. Choi S, Chung M-H. A review on the relationship

between Aloe vera components and their biologiceffects. Seminars in Integrative Medicine . 2003;1(1):53 – 62.16. Cuttle L, Kempf M, Kravchuk O, et al. The efficacyof Aloe vera , tea tree oil and saliva as first aid treatment for

partial thickness burn injuries. Burns . 2008;34(8):1176 – 1182. [PubMed ]17. Maenthaisong R, Chaiyakunapruk N, Niruntraporn S,Kongkaew C. The efficacy of Aloe vera used for burnwound healing: a systematicreview. Burns . 2007;33(6):713 – 718.[ PubMed ]
















18. Zampieri N, Zuin V, Burro R, Ottolenghi A, CamoglioFS. A prospective study in children: pre- and post-surgeryuse of vitamin E in surgical incisions. Journal of Plastic,

Reconstructive and Aesthetic Surgery . 2010;63(9):1474 – 1478. [PubMed ]19. Thiele JJ, Ekanayake-Mudiyanselage S. Vitamin E inhuman skin: organ-specific physiology and considerationsfor its use in dermatology. Molecular Aspects of

Medicine .2007;28(5-6):646 – 667. [PubMed ]20. Endre AB, Hari GG, Hales CA. Chemistry and Biologyof Hyaluronan . Oxford, UK: Elsevier Science; 2004. Ch20: Viscoelastic properties of hyaluronan and itstherapeutic use; pp. 415 – 455.21. Burd DAR, Greco RM, Regauer S, Longaker MT,Siebert JW, Garg HG. Hyaluronan and wound healing: anew perspective. British Journal of PlasticSurgery .1991;44(8):579 – 584. [PubMed ]22. Dong Z, Wang Q, Du Y. Alginate/gelatin blend filmsand their properties for drug controlled release. Journal of

Membrane Science . 2006;280(1-2):37 – 44.23. Cencetti C, Bellini D, Pavesio A, Senigaglia D,Passariello C, Virga A. Preparation and characterization ofantimicrobial wound dressings based on silver, gellan, PVAand borax. Carbohydrate Polymers . 2012;90:1362 – 1370. [PubMed ]24. Aramwit P, Siritienthong T, Srichana T,Ratanavaraporn J. Accelerated healing of full-thicknesswounds by genipin-crosslinked silk sericin/PVA

















31. Cuq B, Gontard N, Cuq J-L, Guilbert S. Selectedfunctional properties of fish myofibrillar protein-basedfilms as affected by hydrophilic plasticizers. Journal of

Agricultural and Food Chemistry . 1997;45(3):622 – 626.32. Irissin-Mangata J, Bauduin G, Boutevin B, Gontard N.

New plasticizers for wheat gluten films. European Polymer Journal . 2001;37(8):1533 – 1541.33. Jimenez-Castellanos MR, Zia H, Rhodes CT.Mucoadhesive drug delivery systems. Drug Developmentand Industrial Pharmacy . 1993;19(1-2):143 – 194.34. Shi C, Zhu Y, Ran X, Wang M, Su Y, Cheng T.Therapeutic potential of chitosan and its derivatives inregenerative medicine. Journal of Surgical

Research .2006;133(2):185 – 192. [ PubMed ]35. Förster T, Jackwerth B, Pittermann W, von RybinskiW, Schmitt M. Properties of emulsions. CosmeticToiletries . 1997;112:73 – 82.36. Csóka I, Csányi E, Zapantis G, Nagy E, Fehér-Kiss A,Horváth G. In vitro and in vivo percutaneous absorption oftopical dosage forms: case studies. International Journal of

Pharmaceutics . 2005;291:11 – 19. [ PubMed ]37. Jacobi U, Weigmann H-J, Ulrich J, Sterry W,Lademann J. Estimation of the relative stratum corneumamount removed by tape stripping. Skin Research andTechnology .2005;11(2):91 – 96. [ PubMed ]38. Padula C, Fulgoni A, Santi P. In vivo stratum corneumdistribution of lidocaine, assessed by tape stripping, from a









new bioadhesive film. Skin Research andTechnology .2010;16(1):125 – 130. [ PubMed ]39. Padula C, Chiapponi C, Dibari MT, et al. Single layer

transdermal film containing lidocaine: water and lidocainemobility determined using neutron scattering. Journal of

Pharmaceutical Sciences . 2010;99(10):4277 – 4284. [PubMed ]40. Shukla A, Rasik AM, Patnaik GK. Depletion ofreduced glutathione, ascorbic acid, vitamin E andantioxidant defence enzymes in a healing cutaneouswound. Free Radical Research . 1997;26(2):93 – 101. [ PubMed ]

Articles from BioMed Research International are provided herecourtesy of Hindawi Publishing Corporation








Documents

polimeric films.docx