In Vitro Evaluation of Pluronic F127-Based Controlled-Release Ocular Delivery Systems for Pilocarpine

Desai, Suketu D.; Blanchard, James

doi:10.1021/js970090e

Cited by 153 publications

(76 citation statements)

References 20 publications

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“…Pluronic F127 is known to provide sustained release and increased stability of drug molecules including peptides 9,11,26 and nonpeptides. 27 Our studies (unpublished data, 2005) on differential scanning analysis of PF127 gels containing Spantide II show no interaction of this peptide with the gel matrix. Therefore, this polymer offers better compatibility and release characteristics of Spantide II.…”

Section: E569mentioning

confidence: 71%

In vitro and in vivo evaluation of topical formulations of Spantide II

et al. 2005

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The purpose of this study was to develop and evaluate topical formulations of Spantide II, a neurokinin-1 receptor (NK-1R) antagonist, for the treatment of inflammatory skin disorders. Spantide II lotion and gel was formulated with and without n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of Spantide II from gels was evaluated using microporous polyethylene and polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous absorption of Spantide II from lotion and gel formulations was evaluated using the above setup by replacing the membranes with hairless rat skin. The in vivo anti-inflammatory activity of Spantide II formulations was evaluated in an allergic contact dermatitis (ACD) mouse model. Among different gels studied, PF127 gel showed highest (70-fold) release of Spantide II compared with hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) gels. Lotion and gel formulations with or without NMP showed no detectable levels of Spantide II in the receiver compartment of the Franz diffusion cell until 24 hours. However, Spantide II showed significant retention in epidermis and dermis from lotion and gel formulations at 24 hours. The dermal levels increased~3.5-and 2-fold when the lotion and gel formulations contained NMP as compared with the formulation with no NMP (P G .05). The in vivo studies indicated that Spantide II formulations with NMP were effective in significantly reducing ACD response, similar to dexamethasone (0.5 mM). In conclusion, Spantide II was stable as a topical formulation and delivered to target skin tissue (epidermis and dermis) for the treatment of ACD. In addition this study supports the role of cutaneous neurosensory system in modulating inflammatory responses in the skin.

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Section: E569mentioning

confidence: 71%

In vitro and in vivo evaluation of topical formulations of Spantide II

et al. 2005

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“…9 The combination of Poloxamer-407 and HPMC provides a drug delivery matrix with slower drug release compared to either component alone. 10,21,25,26 In the present studies, we examined the mobilization properties of Flt3L when formulated in a sustained release matrix composed of Poloxamer-407 and HPMC. Our pharmacokinetic analyses demonstrated that the administration of Flt3L formulated with PG (PG-Flt3L) resulted in sustained delivery.…”

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confidence: 99%

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

Robinson

Chavez

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et al. 2003

Bone Marrow Transplant

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Summary:Fms-like tyrosine kinase (Flt3L) is a potent stimulator of hematopoietic progenitor cell (HPC) expansion and mobilization; however, this requires 7-10 days of administration. We investigated whether sustained delivery of Flt3L using a poloxamer-based matrix (PG) could accelerate and/or improve the hematopoietic activity of Flt3L in mice. A single injection of PG-Flt3L stimulated significantly more rapid and greater HPC mobilization to the spleen and peripheral blood than the daily injection of Flt3L formulated in saline. Pharmacokinetic analysis demonstrated that the formulation of Flt3L in PG prolonged its elimination (Tb) half-life (2.3-fold) and increased its bioavailability (4two fold) and the time to maximum serum concentration (T max ) (2.7-fold). Further, coadministration of G-CSF and PG-Flt3L allowed lower doses of Flt3L to be active, with significantly greater hematopoietic and mobilization activity, compared to the same total dose of G-CSF, Flt3L or G-CSF and Flt3L formulated in saline. These data demonstrate that formulation of Flt3L in PG significantly accelerates and increases HPC expansion and mobilization. The observation of increased bioactivity by PG-Flt3L in rodents suggests the potential for improved clinical efficacy of Flt3L by reducing the time required for HPC mobilization.

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“…The viscosity values of PLO are higher than the rest of the excipients, which substantiates a lesser transfer from this base (Desai and Blanchard 1998). As far as the greater release from the Pluronic gel to that of PLO is concerned, it could be due to the greater filtration of water to the gel, which causes the fragmentation of the latter and complete release of the methimazole (Sambhaji et al 2004).…”

Section: In Vitro Releasementioning

confidence: 96%