Poly (lactic Acid) Nanoparticle Drug Carrier Systems And Their In Vitro Drug Release Behavior

With the remarkable development of nanotechnology in recent years, new drugdelivery approaches based on the state-of-the-art nanotechnology have been receivedintensive attention. Nanoparticles (NPs), an evolvement of nanotechnology, areincreasingly considered as a potential candidate to carry therapeutic agents safely intoa targeted compartment in an organ, particular tissue or cell. NPs generally vary insize from 10 to 1000nm. Due to their diminutive size, they can penetrate acrossbarriers through small capillaries into individual cells to allow efficient drugaccumulation at the targeted locations in the body. By doing so, the therapeutic agenttoxicity is reduced, the drug side effects are decreased and the treatment efficacy isenhanced. After modification, NPs may increase circulation time in vivo and enablethe site targeting. Nowadays, NPs have been realized using a number of materialsincluding polymers, metals, ceramics, and carbon structures. These researches wouldforce the progress of nanobiotechnology and nanomedicine.Gentamincin sulfate (GS) is currently used for treatment of osteomyelities. Thecontrolled release of GS could be realized by fabricating GS-loaded NPs. Besideantibiotics, many therapeutic agents including proteins, DNA, and peptides have alsobeen developed into potent and complex agent. In the common oral doses, theseagents are often destroyed during intestinal transit or inadequately absorbed andtherefore become ineffective. However, attaching these therapeutic agents to NPs maysolve most of these delivery challenges. PLA is one of the most relevant carriercandidates with biodegradable and biocompatible properties, Which has been usedearlier in tissue engineering and controlled drug delivery systems.In this work, we used poly (DL-lactic acid, PLA) as carried matrix and took GSand bovine serum albumin (BSA) as the model drugs. The GS-loaded PLAnanoparticles (GS-PLA-NPs) and BSA-loaded PLA nanoparticles (BSA-PLA-NPs)were prepared,by means of double emulsion and solvent evaporation technique. Thein vitro release of either GS or BSA from the NPs was measured by ultra-violetspectroscopy. The morphology of the NPs was observed by scanning electronmicroscope (SEM) and their size distributions were examined by dynamic lightscattering (DLS). The effects of concentration of PLA, the molecular weight of PLA. the volume ratio of oil phase to water phase, the concentration of PVA and the dosageof emulsifier on the size distribution and drug release behavior have been investigated.Then, orthogonal design was applied to optimize the parameters of the formulation.The conclusions would be drawn as the following:1. According to the orthogonal experiments, the concentration and molecularweight of PLA have the key important influence on the size distributions of the NPsand the ratio of O/W has an obvious influence on the in vitro release of drug from theNPs. The optimum parameters included that the PLA concentration was 3%, theweight of PLA was 50,000, the PVA concentration was 1.5%, the dosage of emulsifierwas 2%, and the ratio of O/W was 1:3.2. The mean size of the GS-PLA-NPs prepared with the optimum conditions was277.2nm, and the embedding ratio was 10.9%. By SEM observation, theGS-PLA-NPs displayed regular spherical shape with smooth surfaces. The releasebehavior of GS from PLA-NPs exhibited a sustained release profile within 28 days.Furthermore, studies on the release in vitro showed that the release kinetics could bedescribed by the Higuchi equation: Q=21.557t^1/2-1.6338 (R²=0.9935).3. The mean size of the BSA-PLA-NPs prepared with the optimum conditionswas 361.5nm, and the embedding ratio was 49.7%. By SEM observation, theBSA-PLA-NPs displayed regular spherical shape with smooth surfaces. The releasebehavior of BSA from PLA-NPs exhibited a sustained release profile within 8 days.