Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics

Abstract

Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using Diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. Significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As main consequence of the plasma polymerisation, the release kinetics was successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 hours delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.

Plasma polymerized C:H:N:O thin films for controlled release of antibiotic substances

“…In the next step, these virtual reservoirs can be covered with a diffusion barrier to control the release process. Allylamine or PEG‐like coating have already been reported as suitable diffusion barriers …”

“…Allylamine or PEG-like coating have already been reported as suitable diffusion barriers. [11,26] Absorbance properties of some polymers can be utilized as reservoir/storage substance. [27] From the practical point of view so-called plasma polymers, that is, materials created from organic vapors or precursors in low-temperature plasma, are considered as a highly promising method for homogeneous coating of substrates.…”

Plasma polymerized bioceramics for drug delivery: Do surface changes alter biological behaviour?

“…For the shortest treatment PP10 the coating was probably partially uneven, and some areas remained partially uncoated, still allowing for water absorption. Following plasma treatments of a total of 20 min or more (PP20, PP30, PP40), the static contact angles of the surface of β-TCP raised to values between 120 and 126º as observed in Labay et al [20]. This is shocking, considering that usually PEG-coatings are hydrophilic (θs < 90º), as confirmed by the contact angle values measured on flat silicon surfaces (Figure 3) with the same plasma coatings which varied between 74 and 79º.…”

“…It seems clear that the thin layer produced here had suitable chemistry allowing, among others the protein adhesion required for further cell attachment, and therefore produced the minimum alterations in the biological behaviour of the samples. Two different antibiotics were selected in this work: gentamicin, a wide spectrum antibiotic that is widely employed in orthopaedics, and ampicillin, which was selected for its wide spectrum of action and as reference for comparison with previous works [20,35]. Both antibiotics followed distinct drug release profiles (Figure 9): On the one hand, ampicillin displayed burst release in the 1st h of release from UT-D β-TCP, and the stationary stage was reached after only 7h.…”

“…Although plasma polymerization is a well-studied field, its application to bioceramics is rather recent. In a recent work, we proposed plasma polymerization of a hydrophilic polyethyleneglycol (PEG)-like layer as a dry method allowing to coat β-TCP [20]. In that work, the coating produced allowed to successfully modify drug release kinetics, avoiding burst release, and slowing down the initial rate of release.…”