Considerations on the Controlled Delivery of Bioactive Compounds through Hyaluronic Acid Membrane.

Ibrahim Isildak,Daniela Mănuc,Corina Marilena Cristache,Tiberiu Totu,Roxana-Mădălina Buga,Fatih Erci,Camelia Cristea,Eugenia Eftimie Totu

doi:10.3390/membranes12030303

Abstract

(1) Background: The standard treatment for periodontal disease, a chronic inflammatory state caused by the interaction between biofilms generated by organized oral bacteria and the local host defense response, consists of calculus and biofilm removal through mechanical debridement, associated with antimicrobial therapy that could be delivered either systemically or locally. The present study aimed to determine the effectiveness of a hyaluronic acid membrane matrix as a carrier for the controlled release of the active compounds of a formulation proposed as a topical treatment for periodontal disease, and the influence of pH on the complex system’s stability. (2) Methods: The obtained hyaluronic acid (HA) hydrogel membrane with dispersed melatonin (MEL), metronidazole (MZ), and tetracycline (T) was completely characterized through FTIR, XRD, thermal analysis, UV-Vis and fluorescence spectroscopy, fluorescence microscopy, zeta potential and dielectric analysis. The MTT viability test was applied to check the cytotoxicity of the obtained membranes, while the microbiological assessment was performed against strains of Staphylococcus spp. and Streptococcus spp. The spectrophotometric investigations allowed to follow up the release profile from the HA matrix for MEL, MZ, and T present in the topical treatment considered. We studied the behavior of the active compounds against the pH of the generated environment, and the release profile of the bioactive formulation based on the specific comportment towards pH variation. The controlled delivery of the bioactive compounds using HA as a supportive matrix was modeled applying Korsmeyer–Peppas, Higuchi, first-order kinetic models, and a newly proposed pseudo-first-order kinetic model. (3) Results: It was observed that MZ and T were released at higher active concentrations than MEL when the pH was increased from 6.75, specific for patients with periodontitis, to a pH of 7.10, characterizing the healthy patients. Additionally, it was shown that for MZ, there is a burst delivery up to 2.40 × 10−5 mol/L followed by a release decrease, while for MEL and T a short release plateau was recorded up to a concentration of 1.80 × 10−5 mol/L for MEL and 0.90 × 10−5 mol/L for T, followed by a continuous release; (4) Conclusions: The results are encouraging for the usage of the HA membrane matrix as releasing vehicle for the active components of the proposed topical treatment at a physiological pH.

Highlights

Controlled drug release, vital for pharmaceutical therapies in healthcare, is a dynamic, either pulsatile or extended-release of active compounds to avoid side effects and maintain a constant, topical, or plasma level of the medication in chronic diseases [1–6].Periodontal disease is a chronic inflammatory state caused by the interaction between biofilms generated by the organized oral bacteria and the local host defense response [7,8].Following the complex physiological processes involved in the periodontal tissue damage, the bone is lost, minerals as calcium ions are released, and the periodontal pocket is formed [9].The standard treatment for periodontitis consists of calculus and biofilm removal through mechanical debridement, associated with antimicrobial therapy that could be delivered either systemically or locally [10]
We proposed using the unmodified hyaluronic acid (HA) for controlled delivery of active topical treatment with action on periodontal pathogens, with anti-inflammatory and regenerative capacity
After the vaporization of the water, there seems to be a very slight change in the mass of the active mixture, seemingly not resembling the thermal behavior of the powder form—Figure S1b. This is due to the high water content that was evaporated in the first stage

Summary

Introduction

Controlled drug release, vital for pharmaceutical therapies in healthcare, is a dynamic, either pulsatile or extended-release of active compounds to avoid side effects and maintain a constant, topical, or plasma level of the medication in chronic diseases [1–6].Periodontal disease is a chronic inflammatory state caused by the interaction between biofilms generated by the organized oral bacteria and the local host defense response [7,8].Following the complex physiological processes involved in the periodontal tissue damage, the bone is lost, minerals as calcium ions are released, and the periodontal pocket is formed [9].The standard treatment for periodontitis consists of calculus and biofilm removal through mechanical debridement, associated with antimicrobial therapy that could be delivered either systemically or locally [10]. Controlled drug release, vital for pharmaceutical therapies in healthcare, is a dynamic, either pulsatile or extended-release of active compounds to avoid side effects and maintain a constant, topical, or plasma level of the medication in chronic diseases [1–6]. Periodontal disease is a chronic inflammatory state caused by the interaction between biofilms generated by the organized oral bacteria and the local host defense response [7,8]. It has been shown that the pH values differ significantly between periodontal pockets and even between readings from the same pocket. Such observations demonstrated that there are very complex physiological processes involved [14,15].

Methods

Results

Discussion

Conclusion