Characterization and optimization of pH-responsive polymer nanoparticles for drug delivery to oral biofilms

Abstract

We previously reported on cationic, pH-responsive p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA) block copolymer micelles with high affinity for dental and biofilm surfaces and efficient anti-bacterial drug release in response to acidic pH, characteristic of cariogenic (tooth-decay causing) biofilm microenvironments. Here, we show that micelle pH-responsive behaviors can be enhanced through alterations in corona:core molecular weight ratios (CCR). Although similarly stable at physiological pH, upon exposure to acidic pH, micelles with CCR of 4.1 were less stable than other CCR examined. Specifically, a ~1.5-fold increase in critical micelle concentration (CMC) and ~50% decrease in micelle diameters were observed for micelles with CCR of 4.1, compared to no changes in micelles with CCR of 0.8. While high CCR was shown to enhance pH-responsive drug release, it did not alter drug loading and dental surface binding of micelles. Diblocks were shown to encapsulate the antibacterial drug, farnesol, at maximal loading capacities of up to ~27 wt% and at >94% efficiencies, independent of CCR or core size, resulting in micelle diameter increases due to contributions of drug volume. Additionally, micelles with small diameters (~17 nm) show high binding capacity to hydroxyapatite and dental pellicle emulating surfaces based on Langmuir fit analyses of binding data. Finally, micelles with high CCR that have enhanced pH-responsive drug release and binding were shown to exhibit greater antibiofilm efficacy in situ. Overall, these data demonstrate how factors essential for nanoparticle carrier (NPC)-mediated drug deliverycan be enhanced via modification of diblock characteristics, resulting in greater antibiofilm efficacy in situ.

Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing

“…80 These observations reveal further insights into the NP/drug interaction, and although not necessary for bone fracture healing, it provides further application of NPs where pH-responsive release is beneficial, such as drug delivery for cancer and acidic milieus of biofilms. 81 …”

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

“…Then Zhou and co-workers optimized the nanoparticles by alterations in core molecular weight ratios (CCR) based on previous studies. The results showed that farnesol loaded nanoparticles with higher CCR, had enhanced pH-responsive drug release and thus exhibited greater antibiofilm efficacy in situ [158]. Behrens also reported chlorhexidine loaded nanoporous silica nanoparticles with the pH-activated release [205].…”

“…Some periodontitis related microbiota have been reported closely related to peri-implants diseases such as Prevotella intermedia (P. intermedia), A. actinomycetemcomitans, P. gingivalis, T. denticola, and T. forsythia. What's more, S. aureus, Candida albicans (C. albicans) have also been detected [156][157][158].…”

Local and targeted drug delivery for bone regeneration

“…These microspheres provide greater control over release versus scaffolds simply impregnated with antibacterial proteins [53]. Additionally, dental biofilms, which also present an acidic environment, were treated with pH-responsive diblock copolymer nanoparticles containing anti-biofilm agents [54,55]. At physiological pH (7.2), 50% of loaded drug was released within 15 h, while at acidic pH (4.5), 50% of loaded drug was released within 7 h. This approach may be useful in combination with or used in lieu of antibiotics to prevent biofilm colonization during bone regeneration [56].…”