ABSTRACT
The objective of this study is to develop resveratrol (RES) loaded polyethylene glycols (PEGs) modified chitosan (CS) nanoparticles (NPs) by ionic gelation method for the treatment of glaucoma. While increasing the concentration of PEG, the particle size and polydispersity index of the formulations increased. Entrapment efficiency and RES loading (RL) of NPs decreased while increasing PEG concentration. The in vitro release of NPs showed an initial burst release of RES (45%) followed by controlled release. Osmolality of formulations revealed that the prepared NPs were iso-osmolar with the tear. Ocular tolerance of the NPs was evaluated using hen's egg test on the chorioallantoic membrane and it showed that the NPs were non-irritant. RES-loaded PEG-modified CS NPs shows an improved corneal permeation compared with RES dispersion. Fluorescein isothiocyanate loaded CS NPs accumulated on the surface of the cornea but the PEG-modified CS NPs crossed the cornea and reached retinal choroid. RES-loaded PEG-modified CS NPs reduced the intra-ocular pressure (IOP) by 4.3 ± 0.5â mmHg up to 8â h in normotensive rabbits. These results indicate that the developed NPs have efficient delivery of RES to the ocular tissues and reduce the IOP for the treatment of glaucoma.
Subject(s)
Chitosan/chemistry , Cornea/chemistry , Delayed-Action Preparations/administration & dosage , Nanocapsules/chemistry , Polyethylene Glycols/chemistry , Stilbenes/administration & dosage , Stilbenes/chemistry , Administration, Ophthalmic , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/chemistry , Animals , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Delayed-Action Preparations/chemistry , Diffusion , In Vitro Techniques , Nanocapsules/administration & dosage , Nanocapsules/ultrastructure , Ocular Absorption , Particle Size , Rabbits , ResveratrolABSTRACT
PURPOSE: Development and evaluation of camptothecin-loaded-microemulsion (ME) and -magnetic microemulsion (MME) for passive/active-targeted delivery to BALB/c mice-bearing breast cancer. METHODS: Based on the pseudo-ternary phase diagrams camptothecin-loaded-MEs and -MMEs were developed using benzyl alcohol:Captex 300 (3:1), TPGS:Tween 80 (2:1) and water. Furthermore, characterized for their droplet size distribution, magnetic susceptibility and effect of droplet size in plasma and evaluated for in vitro and in vivo targeting potential, drug release, haemolytic potential, cytotoxicity, genotoxicity, in vivo biodistribution and lactone ring stability. RESULTS: Drug-loaded MEs showed uniform droplet distribution, extended drug release (76.07 ± 4.30% at 24 h), acceptable level of haemolytic activity (<20%), significant cytotoxicity (129 ± 3.9 ng/mL) against MCF-7 cancer cells and low DNA damage in lymphocytes. Targeting potential of MMEs was documented in 4T1 breast cancer-induced BALB/c mice. MMEs were concentrated more at the target tissue on introduction of external magnetic field. In vivo biodistribution study documented the active targeting of 5067.56 ± 354.72 ng/gm and passive targeting of 1677.58 ± 134.20 ng/gm camptothecin to breast cancer from MME and ME, respectively. Lactone stability study shows around 80% of the lactone stable at 24 h. CONCLUSIONS: Developed ME and MME may act as a promising nanocarrier for efficient targeting of breast cancer tissues.
