The research themes of Dr Mobedi’s team are “In-situ forming implants”, “Microsphere/Macrosphere” and “Tissue engineering”. Some information about these categories has been given below:
In-situ forming implants
In situ forming implants (ISFI) are parenteral liquid drug delivery formulations generating (semi) solid depot after injection via a syringe into the body. ISFI was first studied in the early 1980s with the goal of developing injectable antimicrobial formulations for local treatment of periodontal diseases by Southern Research Institute and then continued by ATRIX laboratories, USA.
Dunn et al. invented the concept of ISFI based on polymer precipitation by solvent exchange in 1990. They dissolved a water-insoluble and biodegradable polymer poly (D, L-lactide) (PLA) or poly (D, L-lactide-co-glycolideA) (PLGA) in a compatible water miscible organic solvent N-methyl pyrrolidone (NMP). Consequently, drug was incorporated into the polymer solution forming a solution or a suspension after mixing.
Injectable in situ forming implants are classified in to five categories, according to their mechanism of depot formation: (1) thermoplastic pastes, (2) in situ cross linked systems, (3) in situ polymer precipitation, (4) thermally induced gelling systems, (5) insitu solidifying organ gels.
After injection of the formulation into the body, the organic solvent diffuses into the surrounding tissues while aqueous body fluid diffuses into organic polymeric phase. This leads to phase separation and polymer precipitation, forming a depot at injection site. The active pharmaceutical ingredients (API) entrapped within the polymer matrix are released by diffusion through the water-pores and by erosion upon polymer degradation. The degradation rate can be adjusted by choosing the appropriate polymer. The polymers proposed are nontoxic and are well tolerated by the body and the system is easy to formulate. The PLGA formulation described above provides a novel approach for a biodegradable implant since it can be easily injected, avoiding the use of surgical procedures.
Until now, ISFI are still attracting considerable attentions from researchers because of their advantageous over the other parenteral drug delivery devices such as liquids, liposomes, emulsions, microspheres, microparticles. Besides dental administration, ISFI has been investigated for applications in cancer treatment, ophthalmic delivery systems, tissue engineering and three-dimensional cell culturing or cell transplantation.
The principal benefits from ISFI are relatively lower production cost and simple manufacturing procedure. Moreover, ISFI (semi) solid reservoir has higher local retention and stable drug distribution, thus provides better-controlled drug release. For these reasons a large number of in situ forming polymeric delivery systems have been developed and investigated for use in delivering a wide variety of drugs.
Microsphere, as carrier for drug is one of the various approaches of drug delivery which maximizes the drug concentration at the target site. Microspheres are defined as structure made up of continuous phase of one or more miscible polymers in which drug particles are dispersed at the molecular or macroscopic level with particle size range of 1-100 µm. Recently microspheres have been used to deliver drugs, vaccines, antibiotics and hormones in a controlled manner.
Different techniques have been tried for the formulation of microspheres using different polymers such as: Single Emulsion Solvent Evaporation Technique, Double Emulsification Technique, Spray Drying Method, Spray Congealing, Melt Dispersion Technique, Coacervation Phase Separation Method, Chemical and Thermal Cross – linking Method and Ionic Gelation Method.
For more information about some of these methods: Electrospray
Controlled or targeted microspheres facilitate the accurate delivery of drug to the target site and enhance the dissolution rate of drugs because of larger surface area, and this drug delivery system acts as a potential system to increase the bioavailability of the drugs. Microspheres also have some disadvantages such as dose dumping, low entrapment and loading efficiency, polymer toxicity, higher cost, few marketed formulations because of difficulties in the scale up techniques from lab scale to industrial scale.
Besides this, microspheres drug delivery system is a promising area for systemic delivery of orally inefficient drugs as well as an attractive alternative for noninvasive delivery of potent peptide and perhaps protein drug molecules.
ISM (in situ forming microparticle) systems are based on an emulsion of an internal drug containing polymer solution and a continuous oil or aqueous phase. After injection, the inner polymeric phase hardens upon contact with body fluids and thus forms in situ microparticles. ISM systems have significantly reduced initial burst release and viscosity (which is primarily controlled by the external phase). Thus, easier injectability and reduced pain has been achieved, compared to use of the polymer solutions (in situ implant systems). Additionally ISMs are multiparticulates, and thus minimize variations in implant morphology (after solidification) and provide more consistent and reproducible drug release profile.
Tissue Engineering is a multidisciplinary field encompassing the principles of bioengineering, cell transplantation, and material science. The goal of tissue engineering is to develop tissue substitutes that may be used to restore, maintain, or improve the function of diseased or damaged human tissues. In tissue engineering, a scaffold is needed to provide a proper substrate for cell attachment, cell proliferation, differentiated function, and cell migration; in other words, the scaffold provides a suitable space in which transplanted cells can grow and new tissues can be implanted.
For obtaining proper tissue ingrowth and ensure desired nutrient and cell delivery using an implanted scaffold, the scaffold must meet certain specifications. The scaffold must provide sufficient mechanical support to maintain stresses and loadings generated during in vitro or in vivo regeneration. In order for tissue engineering to be practical, scaffolds must be developed that approximates natural cell growth.
Porous scaffolds for tissue engineering, such as bone or cartilage regeneration, are usually prefabricated three-dimensional polymer structures. Prefabricated porous scaffolds require invasive surgery to implant them in anatomical sites. It is also time consuming and inconvenient to reshape prefabricated porous scaffolds to suit a specific patient. Implantation of prefabricated porous scaffolds becomes more difficult if the implant sites have limited access or a complex shape. From the foregoing, a porous scaffold that forms in situ at an anatomical site may offer advantages over a prefabricated porous scaffold.