Histological changes over time around the site of sustained release naltrexone-poly(dl-lactide) implants in humans

Hulse, Gary Kenneth; Stalenberg, V.; McCallum, Dugald; Smit, Watske; O'Neil, George; Morris, Noella; Tait, Robert J.

doi:10.1016/j.jconrel.2005.08.001

Cited by 36 publications

(31 citation statements)

References 18 publications

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“…Among polymers, polyesters based on polylactic acid (PLA), polyglycolic acid (PGA), and their copolymers, poly (lactic-co-glycolic) acid (PLGA), are some of the best defined biomaterials as far as design and performance are concerned (Hulse et al, 2005;De et al, 2008). PLGA is FDA-approved biodegradable polymer, which has an excellent biocompatibiltiy.…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Yang¹,

Xie

Mei³

2014

Drug Delivery

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Poly (D,L-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted considerable interest as new delivery vehicles for small molecules, with the potential to overcome issue such as poor drug solubility and cell permeability. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NPs has been introduced as novel carriers for oral delivery. In this study, our aim was to introduce and evaluate the physiochemical characteristics and bioadhesion of positively charged chitosancoated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size distribution, averaging less than 130 nm. CS-PLGA-NPs was positively charged (+42.1 ± 0.4 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs showed a negative surface charge (À2.01 ± 0.3 mV). CS-PLGA-NPs exhibited stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or thienorphine solution. CS-PLGA-NPs were also found to significantly enhance cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of cytotoxicity showed no increase in toxicity in either kind of nanoparticles during the formulation process. The study proves that CS-PLGA-NPs can be used as a vector in oral drug delivery systems for thienorphine due to its positive surface charge and bioadhesive properties.

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Section: Introductionmentioning

confidence: 99%

Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Yang¹,

Xie

Mei³

2014

Drug Delivery

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“…They appear to be generally mild, consistent with the many other studies of implanted polymers, and to resolve steadily over time. 24 A subsequent study 25 using ultrasound rather than histological techniques, came to similar conclusions. After 24 months, very little implant material was seen.…”

Section: Tissue Reactionsmentioning

confidence: 68%

Últimos desarrollos en los implantes y las inyecciones depot de naltrexona; el jovencito de la escalera se está haciendo mayor

Brewer¹,

Streel²

2010

Adicciones

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Implants and depot injections (DI) of naltrexone (NTX) have undergone considerable development since the first commercially available implants appeared in the mid-1990s. In particular, long-acting implants that can deliver relapse-preventing serum NTX levels for around six months have now been subjected to classic randomised controlled trials that have given positive and generally significant results when compared with oral NTX and placebo implants, or with standard post-detoxification care. They also provide lower serum levels that can prevent opiate overdose for several additional months and 3-year mortality rates are similar to those of methadone maintenance treatment (MMT). At least 18 months of antagonist-assisted abstinence may be desirable to normalise new, opiatefree cognitive-behavioural habits and extinguish old, maladaptive ones. We discuss ideological antagonisms between protagonists of MMT and of NTX implants, notably in Australia, but we argue that both treatments can and should co-exist. The main obstacle to the expansion of longacting implant treatment is not the lack of an evidential or theoretical base but the lack of a licensed product. NTX appears to block all opiates if serum levels are adequate and we stress its apparent lack of clinically significant hepatotoxicity. Some patients may need above-average serum levels and occasionally, habitual injectors continue to inject opiates despite experiencing no opiate effects. RESUMEN ABSTRACTLos implantes y las inyecciones depot (ID) de naltrexona (NTX) han experimentado un notable desarrollo desde que aparecieron los primeros implantes comerciales a mediados de los noventa. Específicamente los implantes de larga duración, capaces de proporcionar NTX en suero con niveles capaces de prevenir las recaídas durante unos 6 meses, han sido sometidos recientemente a las clásicas pruebas con control, con resultados positivos y, generalmente, significativamente superiores a la NTX oral o implantes de placebo o tratamientos estándar post desintoxicación. Además proporcionan niveles en sangre suficientes durante varios meses más para prevenir sobredosis por opiáceos. Por otro lado los índices de mortalidad a tres años son similares a los que están en programas de mantenimiento con metadona (PMM). Por lo menos serán necesarios 18 meses de abstinencia con el apoyo de antagonistas para normalizar los nuevos hábitos de comportamiento sin opiáceos y extinguir los viejos hábitos perjudiciales. Se discuten los antagonismos ideológicos que se dan, sobre todo en Australia, entre los protagonistas de PMM y los de implantes de NTX, concluyendo que ambos tipos pueden y deben coexistir. El principal obstáculo para la expansión de los tratamientos con implantes de larga duración no sería pues la falta de evidencia o de base teórica, sino la inexistencia de un fármaco con licencia. NTX parece que bloquea todos los opiáceos si sus niveles en suero son los adecuados; por otro lado debemos tener en cuenta su aparente falta de hepatotoxicidad. Algunos pacientes pueden necesita...

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“…Each implant consists of 10 individual tablets made up of compressed naltrexone-polymer microspheres, coated in polymer, as described previously. 13,14,17 …”

Section: The Implantmentioning

confidence: 99%

“…The implant is currently in phase 2/3 of clinical development for the treatment of heroin dependence, with studies thus far demonstrating efficacy, 12 biocompatibility, and biodegradation. 13,14 While the use of oral naltrexone is emerging as a possible treatment option for amphetamine dependence, the use of monthly or longer sustained release naltrexone preparations have yet to be examined. Such preparations would be expected to increase the efficacy of the drug by eliminating noncompliance issues.…”

Section: Introductionmentioning

confidence: 99%