Abstract
Purpose: :
The objective of this study was to develop thermoresponsive and biodegradable star-branched dendritic polymers as drug carriers for drug delivery across the blood-ocular barriers.
Methods: :
The thermo-responsive and biodegradable star-branched dendritic polymers were synthesized using a combination of solid phase peptide synthesis, ring-opening polymerization and atom transfer radical polymerization techniques. These dendritic polymers contained biodegradable poly-L-lactic acid (PLLA) branches, thermoresponsive poly (N-isopropyl acrylamide) segmants, and poly-L-lysine (PLL) dendrons. Their chemical structure was characterized using 1H-NMR and FT-IR. Their molecule weights were determined using MALDI-TOF. Their thermoresponsive property was measured using both UV-vis spectroscopy (to measure the transmittance) and dynamic light scattering (to measure the hydrodynamic size of the dendritic polymers). In the degradation studies, the viscosity, molecular weight, and chemical structure of the dendritic polymers were monitored using rheometer, MALDI-TOF and FTIR, respectively. Their cytotoxicity to retinal pigment epithelium (RPE) cells was evaluated using the MTT assay. The permeabilities of dendritic polymers across the porcine sclera-choroid-RPE, sclera, and cornea were determined using side-by-side diffusion cells. The DTAF-labeled nanoparticle solutions were added to the donor cell while equal volume of transport buffer was put in the receiver cell. The fluorescence intensity in the receiver cell was assayed for 4 h.
Results: :
1H-NMR, FT-IR and MALDI-TOF confirmed the successful synthesis of the star-branched dendritic polymers. UV-vis spectroscopy and dynamic light scattering measurements showed that they were thermoresponsive with LCSTs around of 30-40 °C at different concentrations (0.05-1mg·mL). Degradation studies showed that both viscosity and molecular weight decreased with time during the degradation course. MTT data indicated that the dendritic polymers were not toxic the retinal pigment epithelium (RPE) cells. The ex-vivo data demonstrated that these dendritic polymers were more permeable to the porcine sclera-choroid-RPE than the control, dextran with a molecular weight of 70,000.
Conclusions: :
The developed thermo-responsive and biodegradable star-branched dendritic polymers showed great potential to be used as drug carriers for deliver drug across the blood-ocular barriers.
Keywords: drug toxicity/drug effects • sclera