Sustained ex vivo skin antiseptic activity of chlorhexidine in poly(ϵ-caprolactone) nanocapsule encapsulated form and as a digluconate
Introduction
Nosocomial infections represent the major source of morbidity and mortality for patients in the intensive care unit [1]. Wearing gloves and hand-washing with antiseptics [2], [3] might circumvent transmission of nosocomial pathogens by hands of health care personnel and/or by the bacterial flora of patient’s skin [4]. Various antiseptics including chlorhexidine have been incorporated into hand-washing agents [5]. However, the frequent use of antiseptics and some scrubbing techniques also have been associated with contact dermatitis and allergies [6]. Therefore, the potential of chlorhexidine incorporated either in liposomes or in microspheres to provide controlled delivery of the drug to skin-associated bacteria (e.g. Staphylococcus epidermidis) and sustained activity against Gram-positive and Gram-negative bacteria was investigated [7], [8]. Liposomes, in spite of some advantages over conventional dosage forms, are limited in their use by low encapsulation efficiency, rapid leakage and poor storage stability [9]. Recently, the use of biodegradable polymeric nanoparticles as drug delivery devices has been extensively reviewed [10], and nanocapsules (i.e. nanoparticles having a polymeric shell and core) have been mainly suggested for drug targeting, sustained release for oral and ocular bioavailability improvement purposes [11].
The aim of the present study was to investigate the potential of chlorhexidine base entrapped into poly(ϵ-caprolactone) (i.e. a biodegradable polyester, PCL) nanocapsules [12] to provide sustained bactericidal activity (i) in vitro against several hospital strains of bacteria by determination of minimal inhibitory concentration (MIC), (ii) ex vivo against Staphylococcus epidermidis (i.e. coagulase-negative Staphylococcus associated with the skin responsible for nosocomial infections) applied to porcine ear skin. The topical antimicrobial efficacy of chlorhexidine base loaded PCL nanocapsules was compared to that obtained with a disinfectant-detergent solution of chlorhexidine digluconate. Furthermore, skin absorption of chlorhexidine from either chlorhexidine base-carrier suspension or chlorhexidine digluconate solution was compared with the effectiveness of the skin antisepsis treatment.
Section snippets
Materials
Chlorhexidine base and PCL (mw: 42 500) was purchased from Sigma–Aldrich (St. Quentin, Fallavier, France). Hibitane® 5% is a commercial chlorhexidine digluconate solution and was provided by Zeneca (Cergy-Pontoise, France). Acetone, acetonitrile, sodium acetate and acetic acid were provided by Prolabo (Lyon, France). Phospholipids (Epikuron® 200) were obtained from Lucas Meyer (St. Maur des Fossés, France). Epikuron® 200 was a purified wax-like phosphatidylcholine of soybean origin, which
Formulation and characterization of chlorhexidine nanocapsules
Table 1 shows the determination of chlorhexidine base loading in PCL nanocapsules from interfacial polymer deposition following solvent displacement method in formulations A and B. Encapsulation efficiency of chlorhexidine base in PCL nanocapsules was 60% whatever the initial chlorhexidine base amount dissolved in the organic mixture. No free chlorhexidine base was detected in both formulations A and B likely probably due to its low water solubility.
PCS was used as a sizing technique to assess
Steric and electrostatic mechanisms of bacterial adhesion
Chlorhexidine base and its salts are widely used as antiseptic, disinfectant, pharmaceutical and cosmetic preservative and antiplaque agents. For skin antisepsis, chlorhexidine has been formulated as a 0.5% (w/v) solution in 70% (v/v) ethanol [21]. However, although chlorhexidine salts are bacteriostatic and bactericidal in low and higher concentrations to many Gram-positive and Gram-negative bacteria, residual antiseptic action on the skin after rinsing and drying was not proven. In our study,
Conclusion
Chlorhexidine base loaded PCL nanocapsules, prepared by interfacial polymer deposition following solvent displacement yields quite uniform size and stable positively charged nanocapsules with good encapsulation efficiency. This in vitro study showed that the encapsulation of chlorhexidine base into PCL nanocapsules maintained an antimicrobial activity against several bacteria suggesting a sustained release of chlorhexidine base from PCL nanocapsules into surrounding medium. Furthermore, a
References (55)
- et al.
Handwashing: a ritual revisited
Crit. Care Nurs. Clin. North Am.
(1995) - et al.
An evaluation of five protocols for surgical handwashing in relation to skin condition and microbial counts
J. Hosp. Infect.
(1997) - et al.
Biodegradable polymeric nanoparticles as drug delivery devices
J. Control. Release
(2001) - et al.
Nanocapsule formation by interfacial polymer deposition following solvent displacement
Int. J. Pharm.
(1989) - et al.
Antimicrobial efficacy of biocides tested on skin using an ex vivo test
J. Hosp. Infect.
(1998) - et al.
Physicochemical characteristics of two pairs of coagulase-negative staphylococcal isolates with different plasmid profiles
Colloids Surf.
(1994) - et al.
Preparation, characterization and cytotoxicity of methylmethacrylate copolymer nanoparticles with a permanent positive surface charge
Int. J. Pharm.
(1997) - et al.
Influence of chlorhexidine species on the liquid crystalline structure of vehicle
Int. J. Pharm.
(2001) - et al.
Changes in bacterial flora associated with skin damage on hands of health care personnel
Am. J. Infect. Control.
(1998) - et al.
Percutaneous absorption of a chlorhexidine digluconate solution
Int. J. Pharm.
(1997)
Vitamin A-loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin
Eur. J. Pharm. Biopharm.
PLGA microparticles: a possible vehicles for topical drug delivery
Int. J. Pharm.
Enhanced transport of nanoparticle associated drugs through natural and artificial membranes—a general phenomenon?
Int. J. Pharm.
Topical application of acyclovir-loaded microparticles: quantification of the drug in porcine skin layers
J. Controlled Release
Nosocomial infection and death in a neonatal intensive care unit
J. Infect. Dis.
Examination gloves as barriers to hand contamination in clinical practice
J. Am. Med. Assoc.
The role of the skin in nosocomial infection: a review
J. Chemther.
Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units
New Engl. J. Med.
The interaction of phospholipid liposomes with bacteria and their use in the delivery of bactericides
J. Drug Targeting
Sustained in vitro activity of human albumin microspheres containing chlorhexidine dihydrochloride against bacteria from cultures of organisms that cause urinary tract infections
Antimicrob. Agents Chemother.
Liposomes as Drug Carriers
Drug-loaded nanoparticles—preparation methods and drug targeting issues
Eur. J. Pharm.
Accelerated degradation of poly(ϵ-caprolactone) by organic amines
Pharm. Res.
Some observations on the formulation and properties of chlorhexidine
J. Soc. Cosmet. Chem.
Determination of the antibacterial efficacy of several antiseptics tested on skin by an ex vivo test
J. Med. Microbiol.
Percutaneous absorption of sunscreens through micro-Yucatan pig skin in vitro
Pharm. Res.
Characterization of the permeability barrier of human skin in vivo
Proc. Natl. Acad. Sci.
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2021, Journal of Drug Delivery Science and TechnologyCitation Excerpt :Due to its accelerated absorption from the capsule wall, one formulation of nanoparticles containing chlorhexidine gluconate (Nanochlorex ®) has an immediate antibacterial effect. It has a long-lasting effect due to continuous release from the particle nucleus [76,77]. Other nanoparticles, such as TiO2, show substantial antibacterial properties after absorbing ultraviolet radiation.