Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model

Date

2003-11-14

Author

Hasırcı, Vasıf Nejat
Goudas, LC
Shuster, L
Carr, DB
Wise, DL

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

64
views

0
downloads

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, I mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.

Subject Keywords

Pain management, Controlled drug release, Hydromorphone, Bupivacaine, Chronic constriction injury

URI

https://hdl.handle.net/11511/32632

Journal

LIFE SCIENCES

DOI

https://doi.org/10.1016/s0024-3205(03)00615-5

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Antioxidant and Antimicrobial Activities of Essential Oils Obtained from Oregano (Origanum vulgare ssp hirtum) by Using Different Extraction Methods KARAKAYA, SİBEL; EL, SEDEF NEHİR; Karagozlu, Nural; Şahin, Serpil (Mary Ann Liebert Inc, 2011-06-01) In this study, antioxidant and antimicrobial activities of essential oils obtained from oregano (Origanum vulgare ssp. hirtum) were determined by using solvent-free microwave extraction (SFME), supercritical fluid extraction, and conventional hydrodistillation (CH) methods. The inhibitory effects on the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical of essential oils obtained from oregano by using SFME and CH were similar. However, essential oil extracted by CH showed greater (2.69 mu mol/mL...
Antibiotic loaded nanocapsules functionalized with aptamer gates for targeted destruction of pathogens Kavruk, M.; ÇELİKBIÇAK, ÖMÜR; Ozalp, V. C.; Borsa, B. A.; Hernandez, F. J.; BAYRAMOĞLU, GÜLAY; SALİH, BEKİR; ARICA, MEHMET YAKUP (2015-01-01) In this study, we designed aptamer-gated nanocapsules for the specific targeting of cargo to bacteria with controlled release of antibiotics based on aptamer-receptor interactions. Aptamer-gates caused a specific decrease in minimum inhibitory concentration (MIC) values of vancomycin for Staphylococcus aureus when mesoporous silica nanoparticles (MSNs) were used for bacteria-targeted delivery.
Antinociceptive effects of hydromorphone, bupivacaine and biphalin released from PLGA polymer after intrathecal implantation in rats Sendil, D; Bonney, IM; Carr, DB; Lipkowski, AW; Wise, DL; Hasırcı, Vasıf Nejat (2003-05-01) Intraspinal drug delivery, based on the concept of controlling pain by delivering drug to a nociceptive target rich in opioid and other relevant receptors is increasingly used clinically. The therapeutic ratio for opioids or other centrally acting agents is potentially greater if they are administered intrathecally (i.t.) than outside the central nervous system (CNS). The present study was designed with the ultimate goal of formulating a controlled release system for intrathecal analgesia characterized by e...
In vivo response to biodegradable controlled antibiotic release systems Korkusuz, F; Korkusuz, P; Eksioglu, F; Gursel, I; Hasırcı, Vasıf Nejat (2001-05-01) In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy-valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone(R) and the Duocid(R)-P(3-HB-co-4-HB) rods with a drug to polymer ra...
Surface functionalization of SBA-15 particles for amoxicillin delivery Sevimli, Filiz; Yılmaz, Ayşen (2012-08-01) The hydrothermally synthesized SBA-15 particles were surface functionalized by post-grafting synthesis method with (3-aminopropyl) triethoxy silane, mercaptopropyl trimethoxy silane and triethoxy methyl silane in order to be used as carrier materials for drug delivery. Amoxicillin was used as a model drug. The adsorption and release properties of calcined and organic-functionalized mesoporous silicas containing terminal primary amine, organothiol and methyl groups toward amoxicillin have been investigated. ...

Citation Formats

V. N. Hasırcı, L. Goudas, L. Shuster, D. Carr, and D. Wise, “Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model,” LIFE SCIENCES, pp. 3323–3337, 2003, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/32632.