The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the ...The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.展开更多
Intrauterine injection and zymography were used to investigate the effect of nitric oxide (NO) on embryo implantation in mice. On day 3, one uterine horn of female pregnant mice was injected intraluminally with variou...Intrauterine injection and zymography were used to investigate the effect of nitric oxide (NO) on embryo implantation in mice. On day 3, one uterine horn of female pregnant mice was injected intraluminally with various doses of nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), while the contralateral horn served as control. Animals were sacrificed by cervical dislocation on day 7 of gestation, and the number of implanted embryos in each horn was calculated. The results showed that lower doses (0.05mg L-NAME) did not inhibit implantation significantly (P 】 0.05), but high doses (0.2 mg L- NAME) resulted in a significant reduction in the number of implanted embryos (P 【 0.05). Co-administration of SNP, a generator of NO, with L-NAME would reverse the anti-implantation effect of L-NAME. To further understand the precise mechanism of NO in implantation, matrix metallo-proteinase (MMPs) activities were detected by gelatin zymography. The reduction in the number of implanted展开更多
文摘The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.
基金This study was supported by the State Major Basic Research Project (Grant No. 1999055903) the Knowledge Innovation Project of the Chinese Academy of Science.
文摘Intrauterine injection and zymography were used to investigate the effect of nitric oxide (NO) on embryo implantation in mice. On day 3, one uterine horn of female pregnant mice was injected intraluminally with various doses of nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), while the contralateral horn served as control. Animals were sacrificed by cervical dislocation on day 7 of gestation, and the number of implanted embryos in each horn was calculated. The results showed that lower doses (0.05mg L-NAME) did not inhibit implantation significantly (P 】 0.05), but high doses (0.2 mg L- NAME) resulted in a significant reduction in the number of implanted embryos (P 【 0.05). Co-administration of SNP, a generator of NO, with L-NAME would reverse the anti-implantation effect of L-NAME. To further understand the precise mechanism of NO in implantation, matrix metallo-proteinase (MMPs) activities were detected by gelatin zymography. The reduction in the number of implanted
