Biomedical subjects

Elvin Blanco

Publications and source records attributed to Elvin Blanco.

5 recordsLinked to original sources

PubMed2007

Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods.

The purpose of this study was to evaluate the antitumor efficacy and local drug distribution from doxorubicin-containing poly(D,L-lactide-co-glycolide) (PLGA) implants for intratumoral treatment of liver cancer in a rabbit model. Cylindrical polymer millirods (length 8 mm, diameter 1.5 mm) were produced using 65% PLGA, 21.5% NaCl, and 13.5% doxorubicin. These implants were placed in the center of VX2 liver tumors (n = 16, 8 mm in diameter) in rabbits. Tumors were removed 4 and 8 days after millirod implantation, and antitumor efficacy was assessed using tumor size measurements, tumor histology, and fluorescent measurement of drug distribution. The treated tumors were smaller than the untreated controls on both day 4 (0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm(2), p = 0.048) and day 8 (0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm(2), p = 0.025). Drug distribution profiles demonstrated high doxorubicin concentrations (>1000 microg/g) at the tumor core at both time points and drug penetration distances of 2.8 and 1.3 mm on day 4 and 8, respectively. Histological examination confirmed necrosis throughout the tumor tissue. Biodegradable polymer millirods successfully treated the primary tumor mass by providing high doxorubicin concentrations to the tumor tissue over an eight day period.

Absorbable Implants↗

PubMed2007

Combined radiofrequency ablation and doxorubicin-eluting polymer implants for liver cancer treatment.

Previously, biodegradable polymer implants (polymer millirods) to release chemotherapeutic agents directly into tumors have been developed. The purpose of this study is to evaluate local drug distribution from these implants in liver tumors treated with radiofrequency (RF) ablation and determine if the implants provide a therapeutic improvement over RF ablation alone. Cylindrical implants were fabricated using 65% poly(D,L-lactide-co-glycolide) (PLGA), 21.5% NaCl, and 13.5% doxorubicin. Control or drug-containing millirods were implanted inside VX2 liver tumors (11 mm diameter) in rabbits after RF ablation. Therapeutic efficacy was assessed 4 and 8 days after treatment using tumor size, histology, and fluorescence measurement of drug distribution. Tumors in both test groups recurred at the boundary of the ablated region. Therapeutic doxorubicin concentrations were found in more than 80% of the ablated area, but concentrations declined rapidly at the boundary between normal and ablated tissue. This region was characterized by a developing fibrous capsule with resolving inflammation, which restricted drug transport out of the ablated zone. The intratumoral doxorubicin implants delivered high concentrations of drug within the ablated region but only limited amounts outside the ablation zone. Future studies will focus on overcoming the fibrotic transport barrier and enhancing drug delivery to the periphery of the ablation region to prevent tumor progression.

Absorbable Implants↗

PubMed2006

Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation.

Recent studies show that after radiofrequency (RF) ablation, fibrosis occurs at the ablation boundary, hindering anticancer drug transport from a locally implanted polymer depot to the ablation margin, where tumors recur. The purpose of this study is to investigate strategies that can effectively deliver dexamethasone (DEX), an anti-inflammatory agent, to prevent fibrosis. Polymer millirods consisting of poly(D,L-lactide-co-glycolide) (PLGA) were loaded with either DEX complexed with hydroxypropyl beta-cyclodextrin (HPbeta-CD), or an NaCl and DEX mixture. In vitro release studies show that DEX complexed with HPbeta-CD released 95% of the drug after 4 days, compared to 14% from millirods containing NaCl and DEX. Rat livers underwent RF ablation and received either DEX-HPbeta-CD-loaded millirods, PLGA millirods with an intraperitoneal (i.p.) DEX injection, or control PLGA millirods alone. After 8 days in vivo, heightened inflammation and the appearance of a well-defined fibrous capsule can be observed in both the control experiments and those receiving a DEX injection (0.29 +/- 0.08 and 0.26 +/- 0.07 mm in thickness, respectively), with minimal inflammation and fibrosis present in livers receiving DEX millirods (0.04 +/- 0.01 mm). Results from this study show that local release of DEX prevents fibrosis more effectively than a systemic i.p. injection.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2006

Modulating beta-lapachone release from polymer millirods through cyclodextrin complexation.

Beta-lapachone (beta-lap) is a novel anticancer agent that kills tumors overexpressing the NADPH: quinone oxidoreductase enzyme. However, poor aqueous solubility and low bioavailability hinder its therapeutic applications. Herein we describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods for local delivery of beta-lap. The objective was to investigate the use of beta-lap inclusion complexes with cyclodextrins (CDs) to control beta-lap release kinetics from PLGA millirods. Differential scanning calorimetry was performed to measure drug/polymer interactions, complexation efficiency with different CDs, and complex/polymer interactions. beta-Lap was found to have a solid-state solubility of 13% in PLGA. beta-Lap dissolution in PLGA matrix lowered the glass transition temperature of PLGA from 44 to 31 degrees C, and led to a slow release of beta-lap (8.8+/-1.2% release after 22 days). For beta-lap and CD interactions, increasing complexation efficiency was observed in the order of alpha-CD, gamma-CD, and beta-CD. beta-Lap complexation with hydroxypropyl-beta-cyclodextrin (HPbeta-CD) prevented drug dissolution in PLGA, and led to fast release (79.6+/-2.1% after 2 days). Sustained drug release was achieved when beta-lap was complexed with alpha-CD or gamma-CD. These data demonstrate the ability to tailor beta-lap release kinetics via CD complexation, providing exciting opportunities for the use of beta-lap-millirods for intratumoral drug delivery.

Antineoplastic Agents↗

PubMed2004

Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers.

In this study, we report the histological findings of a combined therapy using radiofrequency ablation and intratumoral drug delivery in rat livers, with special attention to wound-healing processes and their effects on drug transport in post-ablated tissue. Doxorubicin-loaded millirods were implanted in rat livers that had undergone medial lobe ablation. Millirods and liver samples were retrieved upon animal sacrifice at time points ranging from 1 h to 8 days. Results demonstrate a clearly defined area of coagulative necrosis within the ablation boundary. The wound-healing response, complete with the appearance of inflammatory cells, neovascularization, and the formation of a fibrous capsule, was also observed. At the 8-day time point, fluorescence imaging analysis showed a higher concentration of doxorubicin localized within the ablation region, with its distribution hampered primarily by fibrous capsule formation at the boundary. Given the variant nature of ablated liver, a mathematical model devised previously by our laboratory describes the data well up to 4 days, but loses reliability at 8 days. These results provide useful mechanistic insights into the wound-healing response after radiofrequency ablation and polymer millirod implantation, as well as the impact this natural corollary has on drug distribution.

Animals↗