Zein and hydroxypropyl methylcellulose acetate succinate microfibers combined with metronidazole benzoate and/or metronidazole-incorporated cellulose nanofibrils for potential periodontal treatment.

The development of flexible and porous materials to control antibacterial delivery is a pivotal endeavor in medical science. In this study, we aimed to produce long and defect-free fibers made of zein and hydroxypropyl methylcellulose acetate succinate (HPMCAS) to be used as a platform for the release of metronidazole (MDZ) and metronidazole benzoate (BMDZ) to be potentially used in periodontal treatment. Microfibers prepared via electrospinning under a 2:3 (w/w) zein to HPMCAS ratio, containing 0.5 % (w/w) poly(ethylene oxide) (PEO) and 1 % (w/w) cellulose nanofibril (CNF) were loaded with 40 % (w/w) MDZ, 40 % (w/w) BMDZ, or a combination of 20 % (w/w) of each drug. The addition of CNF improved the electrospinning process, resulting in long fibers with reduced MDZ and BMDZ surface crystallization. MDZ- and BMDZ-incorporated fibers were semicrystalline and displayed commendable compatibility among drugs, nanocellulose and polymeric chains. Release tests showed that zein/HPMCAS/PEO fibers without CNF and with 20 % (w/w) MDZ/ 20 % (w/w) BMDZ released the drug at a slower and more sustained rate compared to other samples over extended periods (up to 5 days), which is a favorable aspect concerning periodontitis treatment.

Herpes Labialis: A New Possibility for Topical Treatment with Well-Elucidated Drugs.

Mucocutaneous infections caused by Herpes simplex virus (HSV-1 and HSV-2) are characterized by the appearance of vesicles that cause pain and embarrassment to the carrier. The standard treatment is based on the use of antivirals in gels or ointments, however, relapses are common. Local anesthetics decrease the pain caused by the lesion, in addition to showing antiviral properties. Semi-solid form facilitates application and its transformation into a thin film favors the maintenance of the formulation in place, with a more discreet final aspect. The objective of this study was to develop and evaluate formulations containing anesthetics for the treatment of cold sores. For this purpose, two semi-solid film-forming formulations were developed and evaluated, containing HPMC K100, lidocaine (LIDO) and prilocaine (PRILO) combined with adjuvants, in the presence (F1T) or not (F1) of the absorption promoter Transcutol®. The mixture of PRILO and LIDO resulted in the formation of a eutectic mixture (EM), essential for penetration of drugs into the skin. The quantification of drugs was performed by HPLC (High Performance Liquid Chromatography), and Transcutol® did not influence the release of drugs from the formulation. The bioadhesiveness of the formulation was evaluate and the drugs did not impair the adhesive potential of the polymers used. The formulations were evaluated in vivo for skin irritation and did not show any negative sign on macroscopic examination. The in vivo efficacy test proved the anesthetics' ability to decrease the lesions caused by HSV-1. Thus, the proposed formulations proved to be good alternatives to the treatment of oral lesions caused by HSV-1.

A New Approach to Ex Vivo Permeation Studies in In-Situ Film-Forming Systems.

The skin is the largest human organ and an important topical route. Even with some challenges, it is an important ally in medication administration, mainly because it is painless and easy-to-apply. Semisolid formulations are the most used dosage forms for drug administration via this delivery route and can be optimized when transformed into a film, favoring on-site maintenance, and promoting drug permeation. However, in situ film-forming systems are difficult to assess and characterize using Franz-type diffusion cells once this apparatus is ideal to formulations without transition phases. The present study proposed a different method to characterize these formulations and provide complementary data on drug and penetration enhancer behaviors, as close as possible to real application conditions. This characterization method allowed us to analyze drug concentration on three necessary occasions: remaining in the polymer film, stratum corneum using adhesive tape, and skin to check where drugs will have a desirable effect. As a proof-of-concept, the proposed ex vivo permeation method was used to evaluate a film-forming system containing lidocaine and prilocaine. We could also evaluate transition phases of drug compositions and quantify drugs at key times after application. Hence, the developed method may be used to provide complementary data to the Franz diffusion cell method, in terms of drug and penetration enhancer behaviors incorporated into film-forming delivery systems.

Effect of Chitosan Dispersion and Microparticles on Older Streptococcus mutans Biofilms.

(1) Background: The effectiveness of chitosan to improve the action of antimicrobial compounds against planktonic bacteria and young biofilms has been widely investigated in Dentistry, where the biofilm lifecycle is a determining factor for the success of antibacterial treatment. In the present study, mature Streptococcus mutans biofilms were treated with chitosan dispersion (CD) or chitosan microparticles (CM). (2) Methods: CD at 0.25% and 1% were characterized by texture analysis, while CD at 2% was spray-dried to form CM, which were characterized with respect to particle size distribution, zeta potential, and morphology. After determining the minimum inhibitory and bactericidal concentrations, S. mutans biofilms were grown on glass slides exposed 8×/day to 10% sucrose and 2×/day to CD or CM at 0.25% and 1%. Biofilm viability and acidogenicity were determined, using appropriate control groups for each experiment. (3) Results: CD had high viscosity and CM were spherical, with narrow size distribution and positive zeta potential. CM affected bacterial viability and acidogenicity in mature S. mutans biofilms more strongly than CD, especially at 1%. (4) Conclusions: Both chitosan forms exerted antimicrobial effect against mature S. mutans biofilms. CM at 1% can reduce bacterial viability and acidogenicity more effectively than CD at 1%, and thereby be more effective to control the growth of mature biofilms in vitro.

Effect of an Experimental Formulation Containing Chlorhexidine on Pathogenic Biofilms and Drug Release Behavior in the Presence or Absence of Bacteria.

(1) Background: For any antibacterial oral formulation to be successful, it must present effects in the presence of biofilms. Therefore, our aim is to analyze the drug release and the antibiofilm effects of a semi-solid formulation containing chlorhexidine (CHX) in the presence of pathogenic biofilms. (2) Methods: The biofilms of Streptococcus mutans (n = 6) or Porphyromonas gingivalis (n = 3) were formed for 6 and 4 days, respectively, being exposed to: 1) a CHX system or 2) vehicle control without CHX. A group without treatment was included as negative control. The acidogenicity, CHX quantification and bacterial viability were determined. A dissolution assay in a buffer and culture medium in the absence of bacteria was also performed. (3) Results: Although the CHX quantification in the culture medium of both biofilms was lower compared to the buffer (p < 0.05) and the culture medium in the absence of bacteria, the CHX system was able to display antibiofilm effects until 96 h for the S. mutans biofilms (p < 0.05) and 72 h for the P. gingivalis biofilms (p < 0.05). (4) Conclusions: The experimental formulation is able to extend chlorhexidine effects, even in challenging conditions such as in the presence of bacteria, allowing the in vitro control of cariogenic biofilms for 4 days and periodontopathogenic biofilms for 3 days.