Enhancement of Bone Formation by Bone Morphogenetic Protein-2 Released from Poly (L-lactic-co-glycolic acid) Microsphere.

An appropriate carrier acting as a sustained delivery vehicle for bone morphogenetic proteins (BMPs) is required for the maximal clinical effectiveness of these osteogenic proteins to enhance bone formation. The purpose of this study was to evaluate a lowmolecular- weight poly(L-lactic-co-glycolic acid) (PLGA) copolymer as a synthetic, biodegradable carrier for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then to address the hypothesis that BMP-2 delivery from this vehicle could promote cell proliferation in vitro and ectopic bone formation in vivo. The BMP-2 was entrapped in microspheres of PLGA by using an improved water-in-oil-in water double-emulsionsolvent- extraction technique. The in vitro release kinetics of rhBMP-2 was determined by ELISA. Then we verified the effect of the sustained delivery vehicle on MSC cell proliferation. The ectopic bone induction in intramuscular implants of mice was evaluated at 2 and 4 weeks post-implantation. The results showed the PLGA microsphere released a total of 14.2%±0.71% rhBMP-2 at the initial phase followed by a prolonged release for 28 days. The rhBMP-2 released from the PLGA microsphere stimulated an increase in alkaline phosphatase (ALP) activity of MSC cells for 5 days in vitro, suggesting that the delivery vehicle releases BMP-2 for a prolonged period in an active form. Moreover, the released rhBMP-2 from the PLGA microsphere significantly promoted MSC cells proliferation after days 5 in culture. In vivo bone formation studies showed the rhBMP-2- loaded PLGA microsphere induced ectopic bone formation to a much greater extent than did rhBMP-2 treated mice. These results demonstrated that the PLGA copolymer material is capable of potentiating the osteogenic efficacy of BMP-2 and, as such, represents a promising delivery vehicle for BMP-2 for orthopedic and dental repair.

Leukemia Therapy: Mechanisms of Drug Resistance and Investigational Strategies.

Certain types of leukemia are amongst the first neoplasias to be “cured” with relatively high 5-year remission rates. This is largely due to targeted therapeutics. However, considerable resistance to tumor-specific targeting drugs has developed due to the presence of abundant cancer stem cells, profound genetic diversity, redundant growth/survival pathways and residual disease. Although these issues propose a challenge, they also provide the opportunity for novel innovations of therapy which currently include the development of multi-target kinase inhibitors, multiple drugs acting on multiple targets, key upstream targets covering multiple downstream targets and the future direction of hybrid molecules targeting two or more targets in different pathways.