(168h) Degradation Kinetics of PLGA and PLGA Conjugated with Alendronate Nanoparticles

A drug carrier has to be able to target, transport and delivery drug to a specific place in the body. This carrier should be degraded by the body as quick as possible in order to avoid accumulation. Also the carrier have to be made from a biodegradable material which could be degraded by the body into nontoxic products. PLGA or poly(lactic-co-glycolic acid) is a biodegradable material used for drug delivery system. This material can be modified with different moieties like alendronate, in order to target to a specific place. Alendronate is a molecule with a higher affinity to bone tissue so, with this material could be possible to target an active compound like N-acetylcysteine to bone tissue. Although, a lot studies has been done about drug delivery systems, only few has been done about degradation of PLGA nanoparticles modified with a particular moiety, and we could not find reports about degradation kinetics of PLGA nanoparticles modified by alendronate (PLGA-ALE). The aim of this research was to compare the degradation kinetic of PLGA, PLGA-ALE and PLGA-ALE-NAC (nanoparticles made with PLGA-ALE and loaded with N-acetylcysteine) nanoparticles, the first one has been reported for many authors, the second and three one has not been reported.

Conjugation of PLGA with alendronate was made by carbodiimide chemistry, joining the acid terminated of PLGA with the amine of alendronate. The reaction was verified by NMR and FTIR. Nanoparticles were produced by nanoprecipitation method. Degradation kinetics was done suspended nanoparticles in PBS at 37 ºC for 33 days, molecular weight of the polymer was measured by GPC.

Polymer degradation exhibited a first order kinetics, with values for the specific kinetics constant of 0.082, 0.0159 y 0.0163 days^-1 for PLGA, PLGA-ALE and PLGA-ALE-NAC nanoparticles respectively. The first value was the highest of the three, which means that alendronate protect polymer chain from a fast degradation. Values of PLGA-ALE and PLGA-ALE-NAC are similar with a difference of 2.5% in favor to PLGA-ALE-NAC indicating a small effect of NAC in favor to polymer degradation. As a conclusion modification of PLGA with alendronate reduce the polymer degradation rate, but, NAC increase 2.5% the degradation rate.