PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.
Ontology highlight
ABSTRACT:
SUBMITTER: Rosario-Melendez R
PROVIDER: S-EPMC3455147 | biostudies-literature | 2012 Sep
REPOSITORIES: biostudies-literature
Publications
PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.
Rosario-Meléndez Roselin R Harris Carolyn L CL Delgado-Rivera Roberto R Yu Lei L Uhrich Kathryn E KE
Journal of controlled release : official journal of the Controlled Release Society 20120803 3
Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, ...[more]
Similar Datasets
Project description:OBJECTIVES:Determine whether an ultrathin biodegradable polymer sirolimus-eluting stent ('Orsiro'-BP-SES) has clinical benefits over second-generation durable polymer drug-eluting stents (DP-DES). METHODS:We conducted a prospective systematic review and meta-analysis of randomised clinical trials comparing Orsiro BP-SES against DP-DES (PROSPERO Registration: CRD42019147136). The primary outcome was target lesion failure (TLF): composite of cardiac death, target vessel myocardial infarction (TVMI) and clinically indicated target lesion revascularisation (TLR)) evaluated at the longest available follow-up. RESULTS:Nine trials randomised 11?302 patients to either Orsiro BP-SES or DP-DES. At mean weighted follow-up of 2.8 years, the primary outcome (TLF) occurred in 501 of 6089 (8.2%) participants with BP-SES compared with 495 of 5213 (9.5%) participants with DP-DES. This equates to an absolute risk reduction of 1.3% in TLF in favour of Orsiro BP-SES (OR 0.82; 95%?CI 0.69 to 0.98; p=0.03). This was driven by a reduction in TVMI (OR 0.80; 95%?CI 0.65 to 0.98; p=0.03). There were no significant differences in other clinical endpoints: cardiac death, TLR and stent thrombosis. CONCLUSION:The Orsiro BP-SES shows promising clinical outcomes in patients undergoing percutaneous coronary intervention compared with contemporary second-generation DES at a short to medium term follow-up. More research is warranted to evaluate performance over a longer follow-up period and in different clinical and lesion subsets.
| S-EPMC7552849 | biostudies-literature
Project description:The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye.
| S-EPMC6722735 | biostudies-literature
Project description:Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain. This review focuses primarily on the preclinical and clinical evidence that support a potential analgesic role for TTX in these pain states. In addition, we also analyze the main toxic effects that this neurotoxin produces when it is administered at therapeutic doses, and the therapeutic potential to alleviate neuropathic pain of other natural toxins that selectively block TTX-sensitive VGSCs.
| S-EPMC8310002 | biostudies-literature
Project description:The extracellular matrix (ECM) has a quasi-ordered reticular mesostructure with feature sizes on the order of tenths of to a few hundred nanometers. Approaches to preparing biodegradable synthetic scaffolds for engineered tissues that have the critical mesostructure to mimic ECM are few. Here we present a simple and general solvent evaporation-induced self-assembly (EISA) approach to preparing concentrically reticular mesostructured polyol-polyester membranes. The mesostructures were formed by a novel self-assembly process without covalent or electrostatic interactions, which yielded feature sizes matching those of ECM. The mesostructured materials were nonionic, hydrophilic, and water-permeable and could be shaped into arbitrary geometries such as conformally molded tubular sacs and micropatterned meshes. Importantly, the mesostructured polymers were biodegradable and were used as ultrathin temporary substrates for engineering vascular tissue constructs.
| S-EPMC3799971 | biostudies-literature
Project description:For over a millennium, mind-body interactions have fascinated scientists and doctors for their abilities to shape human perceptions of the external world 1,2. Placebo effects are striking demonstrations of mind-body interactions in which, in the absence of any treatment, a positive expectation of pain relief can reduce or even abolish the experience of pain 3–6. However, despite widespread recognition of the strength of placebo effects and their impact on everyday human experience and clinical trials for new analgesics, the neural circuit basis of the placebo effect has remained a mystery. Here, we show that analgesia from the expectation of pain relief is mediated by a distinct population of rostral anterior cingulate cortex (rACC) neurons that project to the pontine nuclei (rACC→Pn), a pair of brainstem pre-cerebellar nuclei with no established function in pain processing. To do this, we created a behavioral assay that models placebo analgesia by conditioning mice to expect pain relief when moving from a chamber with a heated floor to a second chamber. In this assay, an expectation of pain relief induces an analgesic effect that, like placebo analgesia in humans, is mediated by endogenous opioids. Calcium imaging of neural activity in freely moving mice and electrophysiological studies in cingulate cortical brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an unusual abundance of opioid receptors in these cells, further suggesting a role in pain modulation. Selective inhibition of either the rACC→Pn pathway or of opioid-receptor-expressing Pn neurons disrupted placebo analgesia and decreased pain thresholds. Finally, a subset of cerebellar Purkinje cells exhibits activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. Altogether, these findings elucidate longstanding mysteries surrounding the placebo effect by identifying a specific neural pathway that mediates expectation-based pain relief. This discovery opens the possibility of targeting this novel pathway with drugs or neurostimulation methods to treat pain. More broadly, our studies provide a framework for investigating the neural circuit basis of other mind-body interactions beyond those involving pain, and point to prefrontocortical-cerebellar communication as a potential basis for such effects.
2024-09-12 | GSE267265 | GEO
Project description:Microcontainers are reservoir-based advanced drug delivery systems (DDS) that have proven to increase the bioavailibity of the small-molecule drugs, targeting of biomolecules, protection of vaccines and improved treatment of Pseudomonas aeruginosa. However, high-throughput loading of these micron-sized devices with drug has been challenging. Hot punching is a new technique that is a fast, simple and single-step process where the microdevices are themselves used as mold to punch biocompatible and biodegradable drug-polymer films, thereby loading the containers. Here, we investigate the effect of hot punching on the drug distribution as well as drug release from the loaded drug-polymer matrices. Zero-order sustained drug release is observed for the model drug Furosemide embedded in biodegradable polymer, Poly-ε-caprolactone, which is attributed to the unique spatial distribution of Furosemide during the loading process.
| S-EPMC7692970 | biostudies-literature
Project description:A fully biodegradable zwitterionic polymer and the corresponding conjugate with paclitaxel (PTX) were synthesized as promising biomaterials. Allyl-functionalized polylactide (PLA) was employed as the precursor of polymer backbones. UV-induced thiol-ene reaction was conducted to conjugate thiol-functionalized sulfobetaine (SB) with the PLA-based backbone. The resulting zwitterionic polymer did not exhibit considerable cytotoxicity. A polymer-drug conjugate was also obtained by thiol-ene reaction of both thiol-functionalized SB and PTX with allyl-functionalized PLA. The conjugate could readily form narrowly-dispersed nanoparticles in aqueous solutions with a volume-average hydrodynamic diameter (Dh,V) of 19.3 ± 0.2 nm. Such a polymer-drug conjugate-based drug delivery system showed full degradability, well-suppressed non-specific interaction with biomolecules, and sustained drug release. In vitro assessments also confirmed the significant anti-cancer efficacy of the conjugate. After 72 h incubation with PLA-SB/PTX containing 10 µg/mL of PTX, the cell viabilities of A549, MCF7, and PaCa-2 cells were as low as 20.0 ± 2.5%, 1.7 ± 1.7%, and 14.8 ± 0.9%, respectively. Both flow cytometry and confocal microscopy suggested that the conjugates could be easily uptaken by A549 cells before the major release of PTX moieties. Overall, this work elucidates promising potentials of biodegradable zwitterionic polymer-based materials in biomedical applications.Statement of significanceThe applicability of FDA-approved biodegradable aliphatic polyesters has been significantly restricted because they are hydrophobic and lack functionalities. Recently zwitterionic polymers have emerged as promising hydrophilic biomaterials, but most of the reported zwitterionic polymers are non-biodegradable. This study reports a novel aliphatic polyester-based zwitterionic polymer and the corresponding polymer-drug conjugate. Their aliphatic polyester and zwitterionic components provide them with high enzymatic degradability and low nonspecific interactions with biomolecules, respectively. While the zwitterionic polymer did not show noticeable cytotoxicity, the corresponding polymer-anticancer drug conjugate exhibited acid-sensitive sustained drug release, remarkable effectiveness in killing cancer cells, as well as the ready cellular internalization. This work lays a foundation for the further development of synthetic biodegradable zwitterionic polymer-based materials which potentially may have broad and significant biomedical applications.
| S-EPMC5682198 | biostudies-literature
Project description:BackgroundsDrug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES.MethodsSystematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included.ResultsEight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848-1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755-1.802; p = 0.487; RR 0.273; 95% CI 0.115-0.652; p = 0.003; p for interaction = 0.003).ConclusionsIn this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up.Prospero register numberhttp://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J.
| S-EPMC3823917 | biostudies-literature
Project description:BackgroundEpidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. This review was originally published in 2006 and was updated in 2012 and again in 2016.ObjectivesTo assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based analgesia for adults undergoing elective abdominal aortic surgery.Search methodsIn the updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and five trial registers in November 2014, together with reference checking to identify additional studies.Selection criteriaWe included all randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adults who underwent elective open abdominal aortic surgery.Data collection and analysisTwo authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data when required. We assessed the level of evidence according to the scale provided by the GRADE working group.Main resultsWe included 15 trials published from 1987 to 2009 with 1498 participants in this updated review. Participants had a mean age between 60.5 and 71.3 years. The percentage of women in the included studies varied from 0% to 28.1%. Adding an epidural to general anaesthesia for people undergoing abdominal aortic repair reduced myocardial infarction (risk ratio (RR) 0.54 (95% confidence interval (CI) 0.30 to 0.97); I(2) statistic = 0%; number needed to treat for one additional beneficial outcome (NNTB) 28 (95% CI 19 to 1423), visual or verbal analogical scale (VAS) scores up to three days after the surgery (mean difference (MD) -1.78 (95% CI -2.32 to -1.25); I(2) statistic = 0% for VAS scores on movement at postoperative day one), time to tracheal extubation (standardized mean difference (SMD) -0.42 (95% CI -0.70 to -0.15); I(2) statistic = 83%; equivalent to a mean reduction of 36 hours), postoperative respiratory failure (RR 0.69 (95% CI 0.56 to 0.85); I(2) statistic = 0%; NNTB 8 (95% CI 6 to 16)), gastrointestinal bleeding (OR 0.20 (95% CI 0.06 to 0.65); I(2) statistic = 0%; NNTB 32 (95% CI 27 to 74)) and time spent in the intensive care unit (SMD -0.23 (95% CI -0.41 to -0.06); I(2) statistic = 0%; equivalent to a mean reduction of six hours). We did not demonstrate a reduction in the mortality rate up to 30 days (RR 1.06 (95% CI 0.60 to 1.86); I(2) statistic = 0%). The level of evidence was low for mortality and time before tracheal extubation; moderate for myocardial infarction, respiratory failure and intensive care unit length of stay; and high for gastrointestinal bleeding and VAS scores.Authors' conclusionsEpidural analgesia provided better pain management, reduced myocardial infarction, time to tracheal extubation, postoperative respiratory failure, gastrointestinal bleeding, and intensive care unit length of stay compared with systemic opioid-based drugs. For mortality, we did not find a difference at 30 days.
| S-EPMC6464571 | biostudies-literature
Project description:ObjectiveTo compare the efficacy and safety of biodegradable polymer drug eluting stents with those of bare metal stents and durable polymer drug eluting stents.DesignMixed treatment comparison meta-analysis of 258,544 patient years of follow-up from randomized trials.Data sources and study selectionPubMed, Embase, and Central were searched for randomized trials comparing any of the Food and Drug Administration approved durable polymer drug eluting stents (sirolimus eluting, paclitaxel eluting, cobalt chromium everolimus eluting, platinum chromium everolimus eluting, zotarolimus eluting-Endeavor, and zotarolimus eluting-Resolute) or biodegradable polymer drug eluting stents, with each other or against bare metal stents.OutcomesLong term efficacy (target vessel revascularization, target lesion revascularization) and safety (death, myocardial infarction, stent thrombosis). Landmark analysis at more than one year was evaluated to assess the potential late benefit of biodegradable polymer drug eluting stents.ResultsFrom 126 randomized trials and 258,544 patient years of follow-up, for long term efficacy (target vessel revascularization), biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.66, 95% credibility interval 0.57 to 0.78) and zotarolimus eluting stent-Endeavor (0.69, 0.56 to 0.84) but not to newer generation durable polymer drug eluting stents (for example: 1.03, 0.89 to 1.21 versus cobalt chromium everolimus eluting stents). Similarly, biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.61, 0.37 to 0.89) but inferior to cobalt chromium everolimus eluting stents (2.04, 1.27 to 3.35) for long term safety (definite stent thrombosis). In the landmark analysis after one year, biodegradable polymer drug eluting stents were superior to sirolimus eluting stents for definite stent thrombosis (rate ratio 0.29, 0.10 to 0.82) but were associated with increased mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents.ConclusionsBiodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven.
| S-EPMC3898413 | biostudies-literature