At present, in Orthopaedics, local administration of antibiotics in the region of infected and necrotic bone and soft tissues is carried out by implanting preloaded PMMA beads or freshly made loaded with antibiotics at the time of surgery. Clearly, antibiotic beads pose evidenced advantages over those systemically administered. Studies have reported the former to produce negligible serum levels, thereby avoiding systemic toxicity^1,2,3. By eliminating the need for iv use, it also decreases duration of hospitalization, patient comfort and overall treatment cost^2,4. PMMA beads however have a limitation in it being non-biodegradable, thereby obviating the need for a second surgery for its extraction. The antibiotic release from PMMA beads is as low as 25% to 50%^5,6. This drawback has kicked development of biodegradable drug delivery vehicles over the past few years.

 The pharmacokinetic profile of hand rolled antibiotic beads is highly variable, due to its varying shape and surface area⁷. In vitro pharmacokinetic and in vivo animal studies have shown the bone concentrate levels above minimum inhibitory concentration for Vancomycin upto 28 days. In vitro studies with high concentrations of Gentamycin and Vancomycin have shown to decrease osteoblastic activity and also cell death in very high concentrations.

In this study highly porous hydroxyapatite (HAP) pellets are produced by a spray drying and granulation method . The porosity in these material are in the range of 30 nanometers. Normally , HAP bodies used for the orthopaedic and dental application have larger pores in the micron scale. It has been found that antibiotics can be loaded into these nanoporous material and hence can be applied as a drug loaded bone filler for various dental and orthopaedic aplcations. Since HAP is fully degradable , removal is not required unlike PMMA beads. Moreover The hydroxyapatite bead implantation is not associated with exothermic reaction hence it is unlikely that the drug will get inactivated by chemical or thermal reaction in the granules. Practically any antibiotic desired according to sensitivity can be loaded into granules. In vitro studies done by Dr Varma shows that significant amount of elution continues from the beads into tissue fluid occurs for 14 days.

References:

^{1. Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibioticimpregnated polymethylmethacrylate beads.  Clin Orthop. 1992; 278:244-252}

^{2. Blaha JD, Calhoun JH, Nelson CL, et al. Comparison of the clinical effi cacy and tolerance of gentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis. Clin Orthop. 1993; 295:8-12}

^{3. Patzakis MJ, Mazur K, Wilkins J, Sherman R, Holtom P. Septopal beads and autogenous bone grafting for bone defects in patients with chronic osteomyelitis.  Clin Orthop. 1993; 295:112-118.}

^{4. Shih HN, Shih LY, Wong YC. Diagnosis and treatment of subacute osteomyelitis.  J Trauma.2005; 58:83-87}

^{5. Rushton N. Applications of local antibiotic therapy.  Eur J Surg Suppl. 1997; 578:27-30.}

^{6. Wilson KJ, Cierny G, Adams KR, Mader JT. Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads.  J Orthop Res. 1988; 6:279-286.}