Glucocorticoids prolong block duration from polymeric microspheres containing bupivacaine, but not from unencapsulated drug. Here we investigate this effect applies to particles with much more rapid drug release and improved long-term biocompatibility. Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3% or 60% (w/w) dipalmitoylphosphatidylcholine (DPPC) spray-dried lipid-protein-sugar particles (LPSPs) containing 10% (w/w) bupivacaine and 0%, 0.05%, or 0.1% (w/w) dexamethasone. Sensory nerve block from bupivacaine-containing 3% and 60% (w/w) DPPC particles without dexamethasone yielded blocks lasting 301 +/- 56 and 321 +/- 127 min, respectively. Addition of 0.05% (w/w) dexamethasone increased block durations to 610 +/- 182 and 538 +/- 222 min, respectively; increasing dexamethasone loading to 0.1% did not further increase duration. One day after injection, dexamethasone-containing particles resulted in lower inflammation scores and capsule thickness than dexamethasone-free particles, but the difference was gone by day 4. Excipient composition had prominent effects at all time points. For all groups, inflammation was largely resolved by 2 weeks after injection. Dexamethasone approximately doubled the duration of nerve block from bupivacaine-loaded LPSPs, while maintaining excellent biocompatibility. Such formulations could be useful in clinical applications when nerve blockade is needed for 24 hours or less.
"The concepts demonstrated here are not limited to electrospun sutures, but could apply to the spectrum of suture/filament production methods and should be amenable to modification by a broad range of ways to control drug release. One can envision sutures that release more than one drug, particularly drug combinations that can have marked synergistic effects on the duration of local anesthesia, such as site 1 sodium channel blockers  , glucocorticoids   or both  . Such combinations would allow the limited payload of sutures to be much more effective. "
[Show abstract][Hide abstract] ABSTRACT: We have developed a local anesthetic-eluting suture system which would combine the function and ubiquity of the suture for surgical repair with the controlled release properties of a biodegradable polymeric matrix. Drug-free and drug-loaded poly(lactic-co-glycolic acid) (PLGA) sutures were fabricated by electrospinning, with or without the local anesthetic bupivacaine. The tensile strength of the electrospun sutures decreased as drug content increased, but strains remained relatively similar across all groups. Sutures released their entire drug payload over the course of 12 days and maintained approximately 12% of their initial tensile strength after 14 days of incubation in vitro. In a rat skin wound model, local analgesia was achieved 1 day after surgery and lasted approximately 1 week in 90% of treated animals (n=10, p<0.05), and all wounds were able to heal normally without the need for further reinforcement. The sutures caused tissue reaction in vivo that was comparable to that seen with a commercially available suture composed of PLGA. Such sutures may enhance perioperative analgesia and mitigate the need for standard postoperative opioid analgesics.
". Using this model, it is possible to calculate the release constant (k) of the polymer-active compound system, and the diffusion exponent (n) characteristic of the release mechanism. A value of n = 0.5 is expected for Fickian diffusion, while values of n = 1.0 and 0.5 < n < 1.0 are expected for Case II diffusion and non-Fickian diffusion, respectively       . The model proposed by Korsmeyer and Peppas  was applied to the release curves in order to characterize the mechanism of release of the herbicide encapsulated in the PHB and PHBV microparticles. "
[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92±0.74 μm and 5.63±0.68 μm, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative.
"In order to investigate the release mechanism of BVC from alginate nanoparticles, we have been applied the following models: zero-order, first-order, Higuchi and Korsmeyer–Peppas (Hariharan et al., 1994; Colombo et al., 1995; Ferrero et al., 2000; Costa & Lobo, 2001; Colombo et al., 2005; Korsmeyer et al., 1983; Korsmeyer and Peppas, 1991). "
[Show abstract][Hide abstract] ABSTRACT: Bupivacaine (BVC; S75–R25, NovaBupi® is an amide-type local anesthetic. Sodium alginate is a water-soluble linear polysaccharide. The present study reports the development of alginate/bis(2-ethylhexyl) sulfosuccinate (AOT) and alginate/chitosan nanoparticle formulations containing BVC (0.5%). The amounts of BVC associated in the alginate/AOT and alginate/chitosan nanoparticles were 87 ± 1.5 and 76 ± 0.9%, respectively. The average diameters and zeta potentials of the nanoparticles were measured for 30 days, and the results demonstrated the good stability of these particles in solution. The in vitro release kinetics showed a different behavior for the release profile of BVC in solution, compared with BVC-loaded alginate nanoparticles. In vitro and in vivo assays showed that alginate–chitosan BVC (BVC(ALG–CHIT)) and alginate–AOT BVC (BVC(ALG–AOT)) presented low cytotoxicity in 3T3-fibroblasts, enhanced the intensity, and prolonged the duration of motor and sensory blockades in a sciatic nerve blockade model.
Journal of Drug Targeting 03/2010; 18(9):688-99. DOI:10.3109/10611861003649738 · 2.74 Impact Factor
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