Poly (DL- Lactide-co-glycol ide)/Noreth isterone Microcapsules: An Injectable Biodegradable Contraceptive

Beck, Lee R.; Pope, Valerie Z.; Flowers, Charles E.; Cowsar, Donald R.; Tice, Thomas R.; Lewis, Danny U.; Dunn, Richard L.; Moore, Alfred; Gilley, Richard M.

doi:10.1095/biolreprod28.1.186

Cited by 95 publications

(28 citation statements)

References 4 publications

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“…The apparent excess production (by about 21%) of nitrite over melatonin can satisfactorily be explained by a slight accumulation of the formed melatonin in the capsules' material (i.e., [melatonin] caps /[melatonin] aq >1), whereas nitrite does not accumulate in the capsules, i.e., its concentration is the same in both phases ([nitrite] caps /[nitrite] aq =1). Noticeably, PLGA is highly effective in transporting hormones [14,25]. Since NOMela-PLGA capsules can be separated from the synthesis solution and thus can be dispersed in any other aqueous solution, the low solubility of NOMela in an aqueous environment is, of course only in principle, no longer a hindrance for its in vivo application.…”

Section: Discussionmentioning

confidence: 99%

“…Characteristics such as biocompatibility and established regulatory approval for clinical use have attracted interest in PLGA for controlled-release applications [27]. A typical implementation was the injection of hormone-loaded PLGA microcapsules into the musculature [14]. Particle size was shown to be an important effector.…”

Section: Discussionmentioning

confidence: 99%

“…Particle size was shown to be an important effector. At optimized conditions, i.e., particle size >10 µm, non-circulating PLGA microcapsules remained active for several months [14,27,28]. Such a strategy might be favorable for the encapsulation of melatonin but not for the chemically labile NOMela.…”

Section: Discussionmentioning

confidence: 99%

“…In order to confect a pharmacological acceptable approach with a prolonged life-time of NOMela, its encapsulation seems to be a promising alternative. In fact, the encapsulation of sparingly water-soluble drugs into biodegradable poly(lactide-co-glycolide) (PLGA) polymers is an established procedure [14][15][16].…”

Section: Nomela R Oh Melatonin R Onomentioning

confidence: 99%

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Encapsulation of N-Nitroso-melatonin with Poly(lactide-co-glycolide)

Kirsch¹,

Korth²,

Fandrey³

et al. 2017

J Biotechnol Biomater

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N-Nitrosomelatonin (NOMela) is well known for its capabilities to transnitrosate nucleophiles such as thiols and ascorbate thereby generating nitric oxide (NO)-releasing compounds. Like molsidomine, NOMela is one of the few NO-releasing substrates not inducing nitrate tolerance and may be therefore highly suitable as NO-therapeutical. As the physical and chemical properties of NOMela do not allow its direct application (oral or intravascular) in animals/ humans, the encapsulation with biodegradable poly(lactide-co-glycolide) (PLGA) polymers was performed and NOreleasing kinetics were studied. NOMela could be successfully encapsulated in PLGA (NOMela-PLGA) with an efficiency of 85% thereby prolonging its half-life time in aqueous solution (e.g. in the cytoplasm of endothelial and smooth muscle cells) about 3-fold. In the presence of "activated hydroxy compounds" like vitamin C and thus under physiological conditions, NOMela-PLGA yielded two therapeutically relevant hormones, melatonin and nitric oxide, via reactions only known (until now) for unencapsulated, freely diffusing NOMela. Importantly, in the absence of any activated hydroxy compound the unwanted hydrolysis reaction of NOMela dominated, generating the non-functional nitrite (and not nitric oxide). These findings suggested that PLGA-encapsulated NOMela will be highly attractive as a novel NO-releasing drug lacking common side-effects of classical NO-releasing molecules such as glyceroltrinitrate.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Nomela R Oh Melatonin R Onomentioning

confidence: 99%

See 2 more Smart Citations

Encapsulation of N-Nitroso-melatonin with Poly(lactide-co-glycolide)

Kirsch¹,

Korth²,

Fandrey³

et al. 2017

J Biotechnol Biomater

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“…3,4 Many amorphous members of the PLA x GA y family have been proposed as suitable matrices for controlled drug delivery, 5 some of them being commercially available (Decapeptyl 1 LP, Zoladex 1 , Enantone 1 , Sandostatine 1 , etc.). [6][7][8] For all these applications, monitoring the fate of degradation products in vitro and in vivo is one of the critical steps to evaluate degradation characteristics and to extend the biocompatibility criterion to degradation products. For the sake of monitoring their fate in complex living systems, degradable polymer chains have to be labelled.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of ³H and fluorescence‐labelled poly (DL‐Lactic acid)

Ponsart

Coudane

Morgat

et al. 2001

Labelled Comp Radiopharmac

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SummaryThe novel polymer modification method based on the activation of an aliphatic polyester chain by using lithium diisopropylamide at low temperature to form a polycarbanion bearing nucleophilic sites in a position a to the carbonyl groups was applied to rac-poly (lactic acid), PLA 50 , to label this polymer with radioactive tritium atoms or with a fluorescent dye. Despite simultaneous partial chain degradation, radioactive PLA 50 and fluorescent PLA 50 with M n ¼ 14 000 g mol À1 , M w =M n ¼ 1:9 and M n ¼ 32 000 g molrespectively, were obtained. The specific activity of the final compound was 3.7 mCi g À1 that squared with 0.3% substitution reaction. The fluorescent polymer was substituted with 0.25% ratio. This work shows that the LDA activation method appears to have considerable potential.

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