Conference on “Innovation in Drug Delivery: Advances in Local …-italy... · 2013. 10. 18. ·...

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Jan Muselík 1 , Ruta Masteiková 1 , Lenka Vinklárková 1 , Tomáš Sopuch 2 1 University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Pharmacy, Palackého tř. 1/3, 612 42 Brno, Czech Republic 2 Holzbecher, Ltd. – Bleaching &Dyeing Plant in Zlíč, 556 03 Česká Skalice – Zlíč, Czech Republic Carboxymethylcellulose (CMC) is a cellulose derivative suitable for the use in a broad range of applications in the food, pharmaceutical, cosmetic, paper and other industries. CMC is non-toxic and is generally considered to be hypoallergenic; therefore it can be applied directly to the human body tissues. CMC in the form of textile fabric may be used as a wound dressing. The ability of CMC to swell and absorb liquids enables to maintain a moist wound environment, which facilitates the wound-healing process. CMC in the form of sodium salt (NaCMC) alone or in combination with other substances has already been used in wound dressings. However, CMC in its acidic form (HCMC) has not been applied as the wound dressing yet. Therefore, the purpose of the study was to understand the potential behavior of both forms of CMC as nonwoven fabric in the conditions of surface wounds. Absorption of fluids during time, pH of surface after application on the wound model as well as mechanical and microscopic properties were evaluated. Methods NaCMC (Hcel NaT) and HCMC (Hcel HT) were tested in vitro using a wound model (Petri dish, sponge, 20 ml of liquid medium). Media used were: purified water, normal saline (0.9% NaCl), buffer solution with pH 7.4, physiological buffer solution with pH 7.2, and solution A (142 mmol Na + and 2.5 mmol Ca 2+ ). Absorption capacity (g/g) was determined by weighting of swelled materials at time intervals: 15 min., 30 min., 1 hour, 3 hours, 5 hours, 8 hours, 24 hours, 3 days, 5 days and 1 week. Surface pH was measured using a contact electrode at time intervals: 15 min., 8 hours, 24 hours, 3 days, 5 days and 1 week. Mechanical properties (tensile strength) were expressed as a power required for the breaking of a single sample (stripe 10x40 mm) in the dry state or after wetting. Non-woven fabrics were wetted on wound model by their placing on the surface for given time, i.e. 30 min. for Hcel NaT and 30 min., 1 day and 3 days for Hcel HT. A non-woven cotton fabric (material for preparation of Hcel) was used for the comparison. Solutions used were physiological buffer solution of pH 7.2 and solution A. A texture analyser BROOKFIELD CT3 was used for measurements. All measurements were made with two different batches of both Hcel HT and Hcel NaT three times (absorptivity and pH) or five times (tensile strength) for each batch, respectively. Results and discussion The highest absorption capacity of NaCMC was observed in purified water and lower in all remaining solutions. Swelling and gelling of NaCMC was fast and without further significant changes during the tested period. On the contrary, the absorption capacity of HCMC was the lowest in water and significantly higher in buffer solutions imitating the wound environment with the gradual swelling and gelling over the time (max. in 24 hours – 3 days). Absorption capacity of NaCMC reached higher values than HCMC. Thus, NaCMC (Hcel NaT) may be used as an absorptive wound dressing, whereas HCMC (Hcel HT) is useful for slightly exuding wounds. Surface pH of NaCMC ranged from neutral to slightly alkaline. HCMC maintained acidic surface pH during the whole evaluation. Therefore, there can be made an assumption that HCMC (Hcel HT) will be able to reduce the pH value of the wound. It was found that both acute and chronic wounds with elevated alkaline pH expressed lower rates of healing 1 . It may be related to the matrix metalloproteinases (MMPs) activity, which is higher at alkaline pH, thus inhibiting wound matrix formation 2 . In addition to the effects on protease activity, other effects of lowering the pH to create a more acidic environment include inhibition of the microorganisms growth, reduction of the toxicity of bacterial end products, enhancing of the destruction of abnormal collagen in the ulcer bed and promotion of angiogenesis 1 . 1) 2) Microscopic appearance of HCMC (Hcel HT) from the cross section (1) and top (2): dry (A), after 15 min. in physiological buffer solution with pH 7.2 (B), after 3 days in physiological buffer solution with pH 7.2 (C) Both NaCMC and HCMC had satisfactory tensile strength in dry as well as wet state. Although the values of tensile strength were worse than in the case of non-substituted non-wave cotton fabric, they provided the materials very good application (and handling) properties even after swelling. HCMC had considerable better mechanical properties after wetting. Conclusion Both NaCMC and HCMC in the form of nonwoven fabric showed suitable and promising properties to be used as the wound dressing for the moist wound healing. HCMC (Hcel HT) may be used as a pH modulating wound dressing. The work was supported by project ALFA TA CR No TA01010244. Literature 1. Gethin G. The significance of surface pH in chronic wounds. Wounds UK, 2007, 3 (3), 52-56. 2. Greener B. et al. Proteases and pH in chronic wounds. J. Wound Care, 2005, 14 (2), 59-61. 3 rd Conference on “Innovation in Drug Delivery: Advances in Local Drug Delivery” 22-25 September, 2013, PISA (Italy)

Transcript of Conference on “Innovation in Drug Delivery: Advances in Local …-italy... · 2013. 10. 18. ·...

Page 1: Conference on “Innovation in Drug Delivery: Advances in Local …-italy... · 2013. 10. 18. · NaCMC (Hcel NaT) and HCMC (Hcel HT) were tested in vitro using a wound model (Petri

Jan Muselík1, Ruta Masteiková1, Lenka Vinklárková1, Tomáš Sopuch2 1University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Pharmacy, Palackého tř. 1/3, 612 42 Brno, Czech Republic

2Holzbecher, Ltd. – Bleaching &Dyeing Plant in Zlíč, 556 03 Česká Skalice – Zlíč, Czech Republic

Carboxymethylcellulose (CMC) is a cellulose derivative suitable for the use in a broad range of applications in the food, pharmaceutical, cosmetic, paper and other industries. CMC is

non-toxic and is generally considered to be hypoallergenic; therefore it can be applied directly to the human body tissues. CMC in the form of textile fabric may be used as a wound

dressing. The ability of CMC to swell and absorb liquids enables to maintain a moist wound environment, which facilitates the wound-healing process. CMC in the form of sodium salt

(NaCMC) alone or in combination with other substances has already been used in wound dressings. However, CMC in its acidic form (HCMC) has not been applied as the wound

dressing yet. Therefore, the purpose of the study was to understand the potential behavior of both forms of CMC as nonwoven fabric in the conditions of surface wounds. Absorption of

fluids during time, pH of surface after application on the wound model as well as mechanical and microscopic properties were evaluated.

Methods

NaCMC (Hcel NaT) and HCMC (Hcel HT) were tested in vitro using a wound model (Petri dish, sponge, 20 ml of liquid medium). Media used were: purified water, normal saline (0.9%

NaCl), buffer solution with pH 7.4, physiological buffer solution with pH 7.2, and solution A (142 mmol Na+ and 2.5 mmol Ca2+). Absorption capacity (g/g) was determined by weighting

of swelled materials at time intervals: 15 min., 30 min., 1 hour, 3 hours, 5 hours, 8 hours, 24 hours, 3 days, 5 days and 1 week. Surface pH was measured using a contact electrode at

time intervals: 15 min., 8 hours, 24 hours, 3 days, 5 days and 1 week. Mechanical properties (tensile strength) were expressed as a power required for the breaking of a single sample

(stripe 10x40 mm) in the dry state or after wetting. Non-woven fabrics were wetted on wound model by their placing on the surface for given time, i.e. 30 min. for Hcel NaT and 30 min.,

1 day and 3 days for Hcel HT. A non-woven cotton fabric (material for preparation of Hcel) was used for the comparison. Solutions used were physiological buffer solution of pH 7.2 and

solution A. A texture analyser BROOKFIELD CT3 was used for measurements. All measurements were made with two different batches of both Hcel HT and Hcel NaT three times

(absorptivity and pH) or five times (tensile strength) for each batch, respectively.

Results and discussion

The highest absorption capacity of NaCMC was observed in purified

water and lower in all remaining solutions. Swelling and gelling of

NaCMC was fast and without further significant changes during the

tested period. On the contrary, the absorption capacity of HCMC was

the lowest in water and significantly higher in buffer solutions imitating

the wound environment with the gradual swelling and gelling over the

time (max. in 24 hours – 3 days). Absorption capacity of NaCMC

reached higher values than HCMC. Thus, NaCMC (Hcel NaT) may be

used as an absorptive wound dressing, whereas HCMC (Hcel HT) is

useful for slightly exuding wounds.

Surface pH of NaCMC ranged from neutral to slightly alkaline. HCMC maintained acidic surface pH

during the whole evaluation. Therefore, there can be made an assumption that HCMC (Hcel HT) will

be able to reduce the pH value of the wound. It was found that both acute and chronic wounds with

elevated alkaline pH expressed lower rates of healing1. It may be related to the matrix

metalloproteinases (MMPs) activity, which is higher at alkaline pH, thus inhibiting wound matrix

formation2. In addition to the effects on protease activity, other effects of lowering the pH to create a

more acidic environment include inhibition of the microorganisms growth, reduction of the toxicity of

bacterial end products, enhancing of the destruction of abnormal collagen in the ulcer bed and

promotion of angiogenesis1.

1) 2)

Microscopic appearance of HCMC (Hcel HT) from the cross section (1) and top (2): dry (A), after 15 min. in physiological buffer solution with pH 7.2 (B), after 3 days in physiological buffer solution with pH 7.2 (C)

Both NaCMC and HCMC had satisfactory tensile strength in dry as well as wet state. Although the values of tensile

strength were worse than in the case of non-substituted non-wave cotton fabric, they provided the materials very

good application (and handling) properties even after swelling. HCMC had considerable better mechanical

properties after wetting.

Conclusion

Both NaCMC and HCMC in the form of nonwoven fabric showed suitable and promising properties to be used as

the wound dressing for the moist wound healing. HCMC (Hcel HT) may be used as a pH modulating wound

dressing.

The work was supported by project ALFA TA CR No TA01010244.

Literature

1. Gethin G. The significance of surface pH in chronic wounds. Wounds UK, 2007, 3 (3), 52-56.

2. Greener B. et al. Proteases and pH in chronic wounds. J. Wound Care, 2005, 14 (2), 59-61.

3rd Conference on “Innovation in Drug Delivery: Advances in Local Drug Delivery”

22-25 September, 2013, PISA (Italy)