Kinetic assessment of iontophoretic delivery efficiency of niosomal tetracycline hydrochloride incorporated in electroconductive gel.

The purpose of this study was to conduct the kinetic assessment of iontophoretic delivery of niosomal tetracycline-HCl formulated in an electroconductive gel. Tween-80 and Span-80 were used to obtain tetracycline-HCl niosomes with an average diameter of 101.9 ± 3.3 nm, a polydispersity index of 0.247 ± 0.004, a zeta potential of - 34.1 mV, and an entrapment efficiency of 70.08 ± 0.16%. Four different gel preparations, two of which contained niosomal tetracycline-HCl, were transdermally delivered using Franz diffusion cells under the trigger effect of iontophoresis, applied at 0.2, 0.5, and 1 mA/cm2 current density. The control group was the passive diffusion results of the preparation made using a tetracycline-HCl-based drug marketed in Turkey. The control group was compared with the groups that contained (a) tetracycline-HCl in an electroconductive gel, (b) the niosomal tetracycline-HCl formulation in water, and (c) the niosomal tetracycline-HCl formulation in the electroconductive gel. The group with the niosomal formulation in the electroconductive gel displayed the highest increase in iontophoretic transdermal delivery relative to the control group, displaying a 2-, 2.1-, and 2.2-fold increase, respectively, by current density. The experimental results of transdermal delivery using the synergistic effect of niosomal formulation in electroconductive gel and the trigger effect of iontophoresis appeared to divert slightly from zero-order kinetics, demonstrating a statistically significant increase in the rate of controlled transdermal drug delivery. Considering that about 20% of the formulation is transdermally delivered in the first half-hour, the iontophoretic transdermal delivery of niosomal tetracycline-HCl can be efficiently used in local iontophoretic therapy.

The consequences of dehydration-hydration on bone anisotropy and implications on the sublamellar organization of mineralized collagen fibrils.

In this study, the effect of dehydration-hydration based sublamellar dimensional change on bone anisotropy was used as a tool to understand sublamellar organization of mineralized collagen fibrils. Bone consists of hydroxyapatite, Type I Collagen, mucopolysaccharides and bone fluid, which associates with bone constituents and improves the mechanical properties of bone. Knowing that dehydration causes dimensional changes comparable to those observed in the mechanical testing of a bone sample, here, the dehydrated organic component of lamellar bone was modelled to contract towards the mineral, forming a contraction vector as the surface normal of the mineral plate. The amount of dehydration based contraction in rotated collagen fibrils was calculated for two models of sublamellar arrangements, namely A and B, where the mineral plate of the 0° (axial, [0 0 1]) sublamellar collagen fibril was oriented respectively along either (0 1 0) or (0 0 1) planes. Projections of sublamellar contraction vectors were denoted as u, v and w displacements at 10°-20°-30° angles and summed to give the lamellar total. Using the total displacements, anisotropy ratios of properties in directions parallel (W) versus perpendicular (U or V) to the osteonal axis were calculated. With dehydration, the osteonal lamellae in Model A (behaving as positive Poisson's ratio material) may display maximal planar expansion (at 1.4%) and peraxial contraction (-0.24%), which may even cause sample warping. The large variation in the wet and dry bone anisotropy ratios of the models demonstrates the effect of collagen orientation on bone mechanics.

Self-assembling antimicrobial peptides on nanotubular titanium surfaces coated with calcium phosphate for local therapy.

Bacterial infection is a serious medical problem leading to implant failure. The current antibiotic based therapies rise concerns due to bacterial resistance. The family of antimicrobial peptides (AMP) is one of the promising candidates as local therapy agents due to their broad-spectrum activity. Despite AMPs receive increasing attention to treat infection, their effective delivery to the implantation site has been limited. Here, we developed an engineered dual functional peptide which delivers AMP as a biomolecular therapeutic agent onto calcium phosphate (Ca-P) deposited nanotubular titanium surfaces. Dual functionality of the peptide was achieved by combining a hydroxyapatite binding peptide-1 (HABP1) with an AMP using a flexible linker. HABP functionality of the peptide provided a self-coating property onto the nano-topographies that are designed to improve osteointegration capability, while AMP offered an antimicrobial protection onto the implant surface. We successfully deposited calcium phosphate minerals on nanotubular titanium oxide surface using pulse electrochemical deposition (PECD) and characterized the minerals by XRD, FT-IR, FE-SEM. Antimicrobial activity of the engineered peptide was tested against S. mutans (gram- positive) and E. coli (gram-negative) both in solution and on the Ca-P coated nanotubular titanium surface. In solution activity of AMP and dual functional peptide have the same Minimum Inhibitory Concentration (MIC) (32 mg/mL). The peptide also resulted in the reduction of the number of bacteria both for E.coli and S. mutans compare to control groups on the surface. Antimicrobial features of dual functional peptides are strongly correlated with their structures suggesting tunability in design through linkers regions. The dual-function peptide offers single-step solution for implant surface functionalization that could be applicable to any implant surface having different topographies.