Parameters affecting the efficacy of a sustained release polymeric implant of leuprolide

Ravivarapu, Harish B.; Moyer, Katie; Dunn, Richard L.

doi:10.1016/s0378-5173(99)00371-3

Cited by 76 publications

(47 citation statements)

References 11 publications

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“…For example, Ravivarapu et al were able to retrieve implants 105 days after administration of in situ forming implants in rats [9]. The shorter residence time of microspheres compared to in situ forming implants shown in our studies is likely to be…”

Section: Duration Of Drug Release From Plga Microspheres and In Situ mentioning

confidence: 46%

“…For example, the in vitro burst release was related to polymer molecular weight [4], solvent nature [4][5][6], presence of additives [7] and polymer concentration [4,6,8]. The duration of drug release in vivo was related to polymer molecular weight [9], polymer nature [10] and drug loading (3 vs 10% studied; [8]. Some of the parameters were found to have no significant effect on duration of implant efficacy when narrower ranges were investigated (3-6% leuprolide acetate drug loading and 40-50% polymer concentration studied [9]).…”

Section: Introductionmentioning

confidence: 99%

“…The duration of drug release in vivo was related to polymer molecular weight [9], polymer nature [10] and drug loading (3 vs 10% studied; [8]. Some of the parameters were found to have no significant effect on duration of implant efficacy when narrower ranges were investigated (3-6% leuprolide acetate drug loading and 40-50% polymer concentration studied [9]). To our knowledge, the influence of drug lipophilicity has not been studied and this is the first report on the effect of drug lipophilicity on release from in situ forming implants.…”

Section: Introductionmentioning

confidence: 99%

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An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots

Deadman

Kellaway

Yasin

et al. 2007

Journal of Controlled Release

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Drug lipophilicity is known to have a major influence on in vivo drug absorption from intramuscularly and subcutaneously administered solutions. Indeed, chemical modification to increase drug lipophilicity is used to enable sustained drug release from solutions. In contrast to the wealth of knowledge on drug release from simple solutions, the influence of drug lipophilicity on its release from controlled release formulations, such as, microparticles and in situ forming depots, have not been systematically studied. Controlled release vehicles are designed to 'control' drug release, hence, in vitro studies show negligible influence of drug lipophilicity on release. The situation could however be different in vivo, due to interactions between the vehicle and biological tissue. We therefore investigated the influence of drug lipophilicity on its in vivo release in rats from two controlled release formulations, PLGA microparticles and in situ forming depots. Both systems exhibited a burst drug release. Subsequent to the burst release, we found that lipophilicity did not influence the rate or extent of drug absorption from the two formulations over a 10-day study period, which would imply that drug partitioning out of the depots was not the main mechanism of drug release from both formulations. This study must however be repeated with a greater number of animals to increase its power.

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Section: Duration Of Drug Release From Plga Microspheres and In Situ mentioning

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots

Deadman

Kellaway

Yasin

et al. 2007

Journal of Controlled Release

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show abstract

“…Furthermore, a few polymers when injected as highly concentrated solutions deposit as gels upon thermal induction. 10,11 Major challenges in insulin delivery are its stability during particle formation, controlled release in optimum concentrations, and the low absorption of insulin in the small intestine.…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of a conjugated poly(lactide-ethylene glycol) nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

Tomar¹,

Tyagi²,

Kumar³

et al. 2013

IJN

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Poly(ethylene glycol) (PEG) and polylactic acid (PLA)-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90-140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH 2 -PEGDA-NH 2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various concentrations of polymers with respect to each other. Incorporation of insulin within the polymeric matrix was modeled using Connolly molecular surfaces. The computational results corroborated the experimental and analytical data. The ability to control blood glucose levels effectively coupled with the nontoxic behavior of the nanoparticles indicates that these nanoparticles are a potential candidate for insulin delivery.

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“…The most popular and biocompatible solvent used is N-methyl-2-pyrrolidone (NMP). [9][10][11][12][13] Poly(d,l-lactide-co-glycolide) (PLGA) is the most successfully used biodegradable and biocompatible polymer because of its two biodegradable hydrolysis products, lactic and glycolic acids (Figure 1). 14 The properties of PLGA that affect drug release, including its molecular weight (MW), lactide/glycolide ratio, and thermal properties, have been thoroughly investigated.…”

Section: Introductionmentioning

confidence: 99%

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

Koocheki

Madaeni²,

Niroomandi³

2011

IJN

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We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly( d , l -lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement.

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Parameters affecting the efficacy of a sustained release polymeric implant of leuprolide

Cited by 76 publications

References 11 publications

An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots

An investigation into the influence of drug lipophilicity on the in vivo absorption profiles from subcutaneous microspheres and in situ forming depots

In vivo evaluation of a conjugated poly(lactide-ethylene glycol) nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

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