Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits.

Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits.

International journal of pharmaceutics (2012-10-20)

Teresa Musumeci, Claudio Bucolo, Claudia Carbone, Rosario Pignatello, Filippo Drago, Giovanni Puglisi

摘要

Melatonin, a neurohormone secreted by the pineal gland, is able to modulate intraocular pressure (IOP). The aim of this study was to generate nanoparticle (NPs) sustained release formulations that allow to extend the pre-corneal residence time of melatonin, thus prolonging its pharmacological effects. Poly(D,L-lactide-co-glycolide) (PLGA) and PLGA-poly(ethylenglycole) (PEG) nanoparticles (NPs) were used to prepare the new melatonin formulations. Mean particle diameter and zeta potential, determined after freeze-drying in the presence of glucose as a cryoprotectant, ranged between 100 and 400 nm and -32.2/-8.2 mV, respectively for PLGA and PLGA-PEG NPs. Melatonin loading ranged between 44% and 80%. DSC analysis showed a homogeneous molecular dispersion of the drug in the NPs matrix. The hypotensive effect was evaluated by measuring IOP during 24h after instillation in the rabbit eye, in comparison with a melatonin aqueous solution at the same concentration (0.08%, w/v). The tested NPs showed good ocular tolerability in rabbit eye using biomicroscopy. Melatonin-loaded PLGA-PEG NPs were the most effective in reducing IOP up to 8h (maximum IOP reduction: 5 mmHg).

材料

货号

品牌

产品描述

719897

Sigma-Aldrich

RESOMER^® RG 502 H，聚（d，L-丙交酯-共-乙交酯）, acid terminated, viscosity 0.16-0.24 dL/g

P2191

Sigma-Aldrich

聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide (50:50), mol wt 30,000-60,000

P1941

Sigma-Aldrich

聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide (75:25), mol wt 66,000-107,000

719900

Sigma-Aldrich

Resomer^® RG 504 H，聚（D,L-丙交酯-co-乙交酯）, acid terminated, lactide:glycolide 50:50, M_w 38,000-54,000

719870

Sigma-Aldrich

Resomer^® RG 503 H，聚(D,L-丙交酯-共-乙交酯), acid terminated, lactide:glycolide 50:50, M_w 24,000-38,000

719919

Sigma-Aldrich

Resomer^® RG 752 H，聚（D,L-丙交酯-co-乙交酯）, acid terminated, lactide:glycolide 75:25, M_w 4,000-15,000

719889

Sigma-Aldrich

Resomer^® RG 502，聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide 50:50, ester terminated, M_w 7,000-17,000

P2066

Sigma-Aldrich

聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide 65:35, M_w 40,000-75,000

430471

Sigma-Aldrich

聚（D,L-丙交酯-co-乙交酯）, ester terminated, M_w 50,000-75,000

739960

Sigma-Aldrich

Resomer^® RG 505，聚（D,L-丙交酯-co-乙交酯）, ester terminated, M_w 54,000-69,000

739944

Sigma-Aldrich

Resomer^® RG 504，聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide 50:50, ester terminated, M_w 38,000-54,000

719927

Sigma-Aldrich

Resomer^® RG 756 S，聚（D,L-丙交酯-co-乙交酯）, ester terminated, lactide:glycolide 75:25, M_w 76,000-115,000

739952

Sigma-Aldrich

Resomer^® RG 503，聚（D,L-丙交酯-co-乙交酯）, lactide:glycolide 50:50, ester terminated, M_w 24,000-38,000

719862

Sigma-Aldrich

共聚物 ^®RG 653 H，聚（D,L-丙交酯-co-乙交酯）, acid terminated, M_w 24,000-38,000

739979

Sigma-Aldrich

Resomer^® RG 858 S，聚(D,L-丙交酯-共-乙交酯), ester terminated, lactide:glycolide 85:15, M_w 190,000-240,000