Novel Polymeric Bioerodable Microparticles for Prolonged-Release Intrathecal Delivery of Analgesic Agents for Relief of Intractable Cancer-Related Pain

Han, Yuxiao; Thurecht, Kristofer J.; Lam, Ai-Leen; Whittaker, Andrew K.; Smith, Maree T.

doi:10.1002/jps.24497

Cited by 25 publications

(35 citation statements)

References 57 publications

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“…Nanoparticles have attracted interest in recent years because these systems act as carriers providing controlled and sustained drug delivery and increasing the drug's bioavailability and mean residence time (Sukhorukov et al, 2005). The pharmacodynamics and pharmacokinetics of nanoparticulated opioids administered by several routes, including orally, have been investigated in numerous species (Mystakidou et al, 2007;Paul-Murphy et al, 2009;Wang et al, 2009;Krugner-Higby et al, 2011;Hoekman et al, 2014;Han et al, 2015;Vazzana et al, 2015). However, to our knowledge, there are no studies reporting the possible antinociceptive effect of methadone administered orally to horses, as free drug or as nanoencapsulated formulation.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses

Crosignani

Luna

Costa

et al. 2017

Vet Pharm & Therapeutics

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We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vd /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses

Crosignani

Luna

Costa

et al. 2017

Vet Pharm & Therapeutics

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“…Importantly, hydromorphone was stable under the scCO 2 processing conditions. Hydromorphone loading at 9. with EE at 92% with these parameters being 4-5 times higher than our previous work using a w/o/w emulsion method (drug loading of 1.6% and EE of 26%) 6 (Table 1). Additionally, the microparticle size was mainly in the range of 20-45 µm after Grinding (Figure 1) which was within our designed size range of 20-60 µm 6 .…”

Section: Resultsmentioning

confidence: 49%

“…Hydromorphone HCl (Sigma Aldrich) was converted to the corresponding free base form by adjusting the pH to ~10 using 2 M NaOH added dropwise 6 . The scCO 2 microparticle manufacturing (CriticalMix) process was optimised according to Whitaker et al 11 .…”

Section: Preparation Of Hydromorphone-loaded Polymeric Microparticlesmentioning

confidence: 99%

“…Hence, new strategies are needed to address this issue of intractable cancer-related pain. One such strategy is the development of sustained-release biodegradable analgesic-containing microparticles for intrathecal injection as a means to produce continuous analgesia for several weeks in patients suffering from severe chronic cancer-related pain 6 . Poly(lactic-co-glycolic acid) (PLGA) based hydromorphone-loaded microparticles were prepared by a water-in-oil-in-water (w/o/w) double-emulsion method because of the safety, biodegradability, and successful application of PLGA in the clinical setting 7 .…”

Section: Introductionmentioning

confidence: 99%

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Sustained-Release Hydromorphone Microparticles Produced by Supercritical Fluid Polymer Encapsulation

Han

Whittaker

Howdle

et al. 2019

Journal of Pharmaceutical Sciences

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Chronic cancer pain remains prevalent and severe for many patients, particularly in those with advanced disease. The effectiveness of analgesic/adjuvant drug treatments in routine practice has changed little in the last 30 years. To address these issues herein, we have developed sustained-release poly(lactic-co-glycolic acid) (PLGA) microparticles of hydromorphone for intrathecal injection aimed at producing prolonged periods of satisfactory analgesia in patients, as a novel strategy for alleviation of intractable cancer-related pain.These hydromorphone-loaded microparticles were produced successfully using organic solvent free supercritical fluid polymer encapsulation. Drug loading at 9.2 % and encapsulation efficacy at 92 % were achieved for particles in the desired size range (20-45µm) with sustained release over a 5 week period in vitro.

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“…Micromolding technique has provided nonspherical microcarriers that release drugs at desired rates . However, such carriers composed of solid compartments are restricted to encapsulate and release hydrophobic drugs; although microgels are able to encapsulate hydrophilic actives, they suffer low loading capacity and significant leakage of encapsulants …”

Section: Introductionmentioning

confidence: 99%

Microfluidic Production of Biodegradable Microcapsules for Sustained Release of Hydrophilic Actives

Lee

Kim

et al. 2017

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Biodegradable microcapsules with a large aqueous lumen and ultrathin membrane are microfluidically designed for sustained release of hydrophilic bioactives using water-in-oil-in-water double-emulsion drops as a template. As a shell phase, an organic solution of poly(lactic-co-glycolic acid) is used, which is consolidated to form a biodegradable membrane. The encapsulants stored in the lumen are released over a long period of time as the membranes degrade. The period can be controlled in a range of -three to five months at neutral pH condition by adjusting membrane thickness, providing highly sustained release and potentially enabling the programed release of multiple drugs. At acidic or basic condition, the degradation is accelerated, leading to the release in the period of approximately two months. As the membrane is semipermeable, the microcapsules respond to the osmotic pressure difference across the membrane. The microcapsules are inflated in hypotonic condition and deflated in hypertonic condition. Both conditions cause cracks on the membrane, resulting in the fast release of encapsulants in a day. The microcapsules implanted in mice also show sustained release, despite the period is decreased to a month. It is believed that the microcapsules are promising for the in vivo sustained release of drugs for high and long-term efficacy.

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Novel Polymeric Bioerodable Microparticles for Prolonged-Release Intrathecal Delivery of Analgesic Agents for Relief of Intractable Cancer-Related Pain

Cited by 25 publications

References 57 publications

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses

Sustained-Release Hydromorphone Microparticles Produced by Supercritical Fluid Polymer Encapsulation

Microfluidic Production of Biodegradable Microcapsules for Sustained Release of Hydrophilic Actives

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