Development of a novel formulation containing poly(d,l-lactide-co-glycolide) microspheres dispersed in PLGA–PEG–PLGA gel for sustained delivery of ganciclovir

Duvvuri, Sridhar; Janoria, Kumar G.; Mitra, Ashim K.

doi:10.1016/j.jconrel.2005.09.002

Cited by 103 publications

(83 citation statements)

References 19 publications

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“…33 Phase-transition studies revealed that polymer concentrations ranging between 20% and 25% w/v form gel at 32°C-60°C. 34 Since the temperature inside the eye ranges from 34.0°C to 37.0°C, such polymeric gels may be appropriate for delivery. Burst release of active ingredients has been considerably retarded when nanoparticles were dispersed in thermosensitive gels.…”

Section: Resultsmentioning

confidence: 99%

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

Jwala

Boddu

Shah

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valine-D-valine-ACV, D-valine-Lvaline-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Methods: Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-co-glycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. Results: L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of Lvaline-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Conclusion: Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration.

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Section: Resultsmentioning

confidence: 99%

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

Jwala

Boddu

Shah

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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“…Ganciclovir-loaded PLGA microspheres were dispersed in a PLGA-PEG-PLGA gel. [99] The microspheres/hydrogel showed a slower release rate compared to that from PLGA microspheres alone. The release of levonorgestrel, interleukin-2, and ceftazidime from a PLGA-PEG-PLGA hydrogel was reported.…”

Section: Temperature-sensitive Block Copolymer Hydrogelsmentioning

confidence: 94%

“…Temperature-sensitive PEG-PLLA-PEG FITC-labeled dextran [9] PEG-PLGA-PEG Spironolactone, ketoprofen [91] Plasmid DNA [92] Plasmid TGF-b1 [93] FITC [94] PLGA-PEG-PLGA Insulin [95] (ReGel 1 ) GLP-1 [96] Testosterone [97] Indomethacin, 5-fluorouracil [98] Ganciclovir [99] Levonorgestrel, interleukin-2,…”

Section: Hydrogel Types Polymer Delivery/applications Referencesmentioning

confidence: 99%

Injectable Biodegradable Hydrogels

Nguyen

Lee

2010

Macromolecular Bioscience

416

343

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Injectable biodegradable copolymer hydrogels, which exhibit a sol–gel phase transition in response to external stimuli, such as temperature changes or both pH and temperature (pH/temperature) alterations, have found a number of uses in biomedical and pharmaceutical applications, such as drug delivery, cell growth, and tissue engineering. These hydrogels can be used in simple pharmaceutical formulations that can be prepared by mixing the hydrogel with drugs, proteins, or cells. Such formulations are administered in a straightforward manner, through site‐specific control of release behavior, and the hydrogels are compatible with biological systems. This review will provide a summary of recent progress in biodegradable temperature‐sensitive polymers including polyesters, polyphosphazenes, polypeptides, and chitosan, and pH/temperature‐sensitive polymers such as sulfamethazine‐, poly(β‐amino ester)‐, poly(amino urethane)‐, and poly(amidoamine)‐based polymers. The advantages of pH/temperature‐sensitive polymers over simple temperature‐sensitive polymers are also discussed. A perspective on the future of injectable biodegradable hydrogels is offered.magnified image

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“…They are hydrolyzed and metabolized without direct toxic reactions to living tissues. 35 By changing physicochemical properties, such as molecular weight, hydrophilicity and the ratio of lactide to glycolide, 34,36 the degradation rate of PLGA polymer enables the delivery of encapsulated drug to be modulated in a slow and extended intracellular release manner. Besides, antigens or DNA fragments encapsulated in PLGA matrix can be protected from endonuclease activity.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1a (HIF-1a) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1a NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1a NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1a NPs group (Po0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF1a NPs-treated group was significantly smaller than other groups (Po0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1a NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

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Development of a novel formulation containing poly(d,l-lactide-co-glycolide) microspheres dispersed in PLGA–PEG–PLGA gel for sustained delivery of ganciclovir

Cited by 103 publications

References 19 publications

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

Injectable Biodegradable Hydrogels

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

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