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PubMed1998

Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation.

Thyrotropin-releasing hormone (TRH; Protirelin) is an endogenous neuropeptide known to have anticonvulsant effects in several seizure models and in intractable epileptic patients. Like most neuropeptides, its duration of action may be limited by a lack of sustained site-specific bioavailability. To attempt to provide long-term delivery, we attached TRH to a biodegradable polyanhydride copolymer as a sustained-release carrier. Utilizing the rat kindling model of temporal lobe epilepsy, a single TRH microdisk implanted stereotaxically into the seizure focus (amygdala) significantly suppressed kindling expression when assessed by the number of stimulations required to reach each behavioral stage and to become fully kindled (8.63 +/- 0.92 vs. 16.17 +/- 1.37; Mean +/- S.E.M.). Two indices of seizure severity, afterdischarge duration (Mean +/- S.E.M., sec.) (stimulated amygdala [87.40 +/- 5.47 vs. 51.80 +/- 15.65] and unstimulated amygdala [89.60 +/- 5.55 vs. 48.67 +/- 15.8] and clonus duration (71.2 +/- 5.94 vs. 29.40 +/- 8.87; Mean +/- S.E.M., sec.), were also significantly reduced by a single polymeric-TRH implant. Fifty days after initiation of the study a significant reduction in clonus duration (53.90 +/- 3.27 vs. 40.09 +/- 4.14) still remained in the TRH-implanted groups. This report is the first to provide evidence in support of in situ microdisk pharmacotherapy for potential neuropeptide delivery in intractable epilepsy and possibly other neurological disorders.

Animals↗
PubMed1988

Selective cell transplantation using bioabsorbable artificial polymers as matrices.

To date, selective cell transplantation has involved injecting cell suspensions into tissues or the vascular system. This study describes attaching cell preparations to bioerodable artificial polymers in cell culture and then implanting this polymer-cell scaffold into animals. Using standard techniques of cell harvest, single cells and clusters of fetal and adult rat and mouse hepatocytes, pancreatic islet cells, and small intestinal cells have been seeded onto biodegradable polymers of polyglactin 910, polyanhydrides, and polyorthoester. Sixty-five fetuses and 14 adult animals served as donors. One hundred fifteen polymer scaffolds were implanted into 70 recipient animals: 66 seeded with hepatocytes; 23 with intestinal cells and clusters; and 26 with pancreatic islet preparations. The cells remained viable in culture, and in the case of fetal intestine and fetal hepatocytes, appeared to proliferate while on the polymer. After four days in culture, the cell-polymer scaffolds were implanted into host animals, either in the omentum, the interscapular fat pad, or the mesentery. In three cases of fetal intestinal implantation coupled with partial hepatectomy, successful engraftment occurred in the omentum, one forming a visible 6.0 mm cyst. Three cases of hepatocyte implantation, one using adult cells and two using fetal cells, have also engrafted, showing viability of hepatocytes, mitotic figures, and vascularization of the cell mass. To date, no pancreatic islets have survived implantation. This method of cell transplantation, which we have termed "chimeric neomorphogenesis," is an alternative to current methods and requires further study.

Animals↗
PubMed2001

Microphase separation in bioerodible copolymers for drug delivery.

This research examines the microstructure of bioerodible polyanhydrides with an eye towards precise design of drug delivery devices. Our main hypothesis is that the bioerodible copolymer poly(1,6-bis-p-carboxyphenoxyhexane-co-sebacic anhydride) (CPH : SA) undergoes micro-phase separation at certain copolymer compositions due to differences in relative hydrophobicity of the co-monomers, resulting in thermodynamic partitioning of drugs incorporated into these copolymers. We investigate the thermal properties, degree of crystallinity, and surface microstructure of several compositions of CPH : SA using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and atomic force microscopy (AFM). We observe that the degree of crystallinity decreases, while the crystal lamellar thickness increases with CPH content. Phase-imaging using AFM indicates the presence of micro-domains in 20 : 80 and 80 : 20 CPH : SA, while poly(SA) and 50 : 50 CPH : SA show no micro-phase separation. Finally, drug-polymer interactions are studied by loading the polymers with different amounts of brilliant blue (hydrophilic) and p-nitroaniline (hydrophobic). DSC and WAXD analysis shows that loading hydrophobic drugs into relatively hydrophobic polymers (poly(SA)) lowers melting point that becomes more pronounced with increased drug loading.

Biodegradation, Environmental↗
PubMed2002

Why degradable polymers undergo surface erosion or bulk erosion.

A theoretical model was developed that allows to predict the erosion mechanism of water insoluble biodegradable polymer matrices. The model shows that all degradable polymers can undergo surface erosion or bulk erosion. Which way a polymer matrix erodes after all depends on the diffusivity of water inside the matrix, the degradation rate of the polymer's functional groups and the matrix dimensions. From these parameters the model allows to calculate for an individual polymer matrix a dimensionless 'erosion number' epsilon. The value of epsilon indicates the mode of erosion. Based on epsilon, a critical device dimension Lcritical can be calculated. If a matrix is larger than Lcritical it will undergo surface erosion, if not it will be bulk eroding. Lcritical values for polymers were estimated based on literature data. Polyanhydrides were found to be surface eroding down to a size of approximately Lcritical = 10(-4) m while poly(alpha-hydroxy esters) matrices need to be larger than Lcritical = 10(-1) m to lose their bulk erosion properties. To support our theoretical findings it was shown experimentally that poly(alpha-hydroxy ester) matrices, which are considered classical bulk eroding materials, can also undergo surface erosion.

Biocompatible Materials↗
PubMed2003

Crystalline and dynamic mechanical behaviors of synthesized poly(sebacic anhydride-co-ethylene glycol).

A novel biomaterial: poly(sebacic anhydride-co-ethylene glycol) was synthesized by introducing poly(ethylene glycol) (PEG) into a polyanhydride system. This copolymer was synthesized using sebacic acid and PEG via melt-condensation polymerization. The crystalline behavior of these synthesized products was studied, and compared to that of polymer blends of poly(sebacic anhydride) (PSA) and PEG. The crystallinity of PSA chain segments can be significantly enhanced by increasing chain mobility via the introduction of PEG. The crystallinity of the PSA component in copolymers was substantially greater than that of blends. However, the crystalline growth of the PEG segments was totally hindered by the presence of PSA chain segments, such that no crystal for PEG component was found in these copolymers. Besides, a dynamic mechanical analysis of these materials was also performed to provide additional information concerning visco-elastic behavior for other biomedical applications, where it was found that the viscous behavior in copolymers was more significant than in neat PSA and PEG.

Anhydrides↗
PubMedDate not supplied

Degradation of porous poly(anhydride-co-imide) microspheres and implications for controlled macromolecule delivery.

The degradation properties of porous microspheres made using a new family of polyanhydride copolymers, the poly(anhydride-co-imides), were studied. Poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxyphenoxy)propane] microspheres, with and without entrapped bovine serum albumin (BSA) as a model protein, were made using the double emulsion solvent evaporation process. Water penetration and anhydride bond cleavage (polymer degradation) occurred rapidly (< 5 days) compared to the time scale of overall microsphere erosion (weeks to months) with most polymer compositions. Subsequent to bond cleavage, the ultimate erosion of the microsphere and release of entrapped BSA was due mainly to the slow dissolution of the individual hydrophobic monomers (TMA-Tyr, SA and CPP) from the microsphere surface. BSA was released at approximately the same rate as the polymer eroded. Due to the fast degradation of anhydride bonds relative to microsphere erosion, initial polymer molecular weight did not have a significant effect on macromolecule release rates. Instead, monomer solubility correlated well with polymer erosion and BSA release rates. This erosion mechanism leads to predictable drug release rates which may be appropriate for the delivery of many protein therapeutics, including vaccine antigens. The anhydride-imide copolymers were well tolerated in acute toxicity studies in rats and therefore show promise as biomaterials.

Animals↗
PubMed1998

Degradation of double-walled polymer microspheres of PLLA and P(CPP:SA)20:80. I. In vitro degradation.

Double-walled (DW) polymer microspheres with a core of poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride)20:80 (P(CPP:SA)20:80) and an external coat of poly(L-lactic acid) (PLLA) were degraded for up to 6 months in vitro. The effects of hydrolytic degradation on the polymers were studied by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), gel permeation chromatography (GPC) and scanning electron microscopy (SEM). The inner core of the polyanhydride copolymer (P(CPP:SA)20:80) degraded first, breaking down into oligomers during the first week and then into monomers which were trapped by the outer shell of PLLA, crystallized, and remained in the core for the duration of the study. As expected, the PLLA coat degraded at a slower rate due to the ester bonds between lactic acid monomers being more hydrolytically resistant than the anhydride bonds. The PLLA in the DW microspheres decreased from its original molecular weight (Mw) of 24,000 g mol(-1) to approximately 5,000 g mol(-1) over the 6 month study. The melting temperature of the PLLA decreased more than 30 degrees C during the study, but no changes were observed in the FTIR spectra. The 6 month samples were very brittle, showing the concomitant drop in mechanical strength with the decrease in Mw.

Biocompatible Materials↗
PubMed1987

Glaucoma filtration surgery in rabbits using bioerodible polymers and 5-fluorouracil.

A prospective, randomized, double-masked, and placebo-controlled study was performed to examine the effect of a localized and sustained delivery of 5-fluorouracil (5-FU) on the success of glaucoma filtration surgery in 18 rabbits. A bioerodible polyanhydride composed of bis (p-carboxyphenoxy) hexane (PCPH) and sebacic acid (SA) was used as the drug carrier. The polymer and 5-FU (10% by weight) were molded into 4-mm long cylinders by a 15-gauge needle. These implants, with and without the therapeutic agent, were placed at the site of filtration surgery intraoperatively. The results showed that intraocular pressures (IOPs) were lower in the experimental eyes during the second postoperative week, but eventually both experimental and control eyes returned to preoperative levels. Filtration blebs lasted longer in experimental eyes and bleb failure occurred before IOP failure in both experimental and control eyes. Implant disappearance occurred after IOP and bleb failure. Experimental eyes had more postoperative complications than control eyes. Eventually, the filtration surgery failed in both the experimental and control rabbit eyes.

Animals↗
PubMed2001

Programmable biodegradable implants.

Pulsatile release implants were developed that release substances up to 58 days post implantation. With a cylindrical size of 2 mm diameter and 1.8 mm height the matrices can carry as much as 1 mg of drug and allow even for intracranial implantation into a rodent model. The matrices are made of materials that have been used for parenteral applications in humans before such as surface eroding polyanhydrides and bulk eroding poly(D,L-lactic acid) or poly(D,L-lactic acid-co-glycolic acid). The onset of drug release is controlled by the degradation of bulk eroding polymers which are known to exhibit a certain stability over a defined period of time and which start eroding after they reach a critical degree of degradation. The time of drug release onset was found to depend on the molecular weight and the chemical state of the carboxylic acid end of the polymer chain. For testing the onset of release in vivo a nude mouse model was developed where the release of Evan's blue could be observed visually after subcutaneous application. By combining individual matrices with different release onset, a therapeutic system can be composed that releases drugs after implantation at predetermined time points in a preprogrammed way. Potential applications for such matrices is vaccination and local tumor therapy.

Absorbable Implants↗
PubMed1999

Poly(fumaric-co-sebacic anhydride). A degradation study as evaluated by FTIR, DSC, GPC and X-ray diffraction.

The degradation of three poly(fumaric-co-sebacic anhydride) [P(FA:SA)] copolymers is examined in a composition of microspheres made by the hot melt encapsulation process. The emergence of low molecular weight oligomers occurs during degradation of the copolymer microspheres, as evidenced by a variety of characterization methods. Characterization was conducted to determine the extent of degradation of the polyanhydride microspheres using Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction. It is demonstrated that degradation of P(FA:SA) is greatly accelerated at basic pH, yet there is little difference between degradation in neutral and acidic buffers. A good correlation exists between the results of each characterization method, which allows a better understanding of the degradation process and the resulting formation of low molecular weight oligomers in poly(fumaric-co-sebacic anhydride).

Anhydrides↗
PubMed2000

Nanosphere based oral insulin delivery.

Zinc insulin is successfully encapsulated in various polyester and polyanhydride nanosphere formulations using Phase Inversion Nanoencapsulation (PIN). The encapsulated insulin maintains its biological activity and is released from the nanospheres over a span of approximately 6 h. A specific formulation, 1.6% zinc insulin in poly(lactide-co-glycolide) (PLGA) with fumaric anhydride oligimer and iron oxide additives has been shown to be active orally. This formulation is shown to have 11.4% of the efficacy of intraperitoneally delivered zinc insulin and is able to control plasma glucose levels when faced with a simultaneously administered glucose challenge. A number of properties of this formulation, including size, release kinetics, bioadhesiveness and ability to traverse the gastrointestinal epithelium, are likely to contribute to its oral efficacy.

Administration, Oral↗
PubMed1998

The preparation and characterization of polymeric antigen delivery systems for oral administration.

Although polymeric delivery systems are well established for the oral administration of conventional drugs, they have not yet been commercially developed for vaccine delivery. The problems inherent with the oral route of delivery, including low pH, gastric enzymes, rapid transit and poor absorption of large molecules, has made the goal of oral delivery of antigens very challenging. Nevertheless, several polymeric delivery systems for the oral administration of vaccines are currently being evaluated, including microencapsulation in poly(lactide-co-glycolides), alginates, polyanhydrides, starch, polymethacrylates, polyamino acids and enteric coating polymers. These approaches are designed to protect the antigen in the gut, to target the antigen to the gut-associated lymphoid tissue, or to increase the residence time of the antigen in the gut through bioadhesion. Each of these approaches is discussed in relation to antigen encapsulation and integrity, process reproducibility, ease of preparation and encapsulation efficiency. Potential problems associated with the scale-up of these approaches are also briefly addressed. Of particular relevance are the prospects for the application of these formulation processes for commercial development.

Journal Article↗
PubMed2002

Tumor treatment by sustained intratumoral release of 5-fluorouracil: effects of drug alone and in combined treatments.

PURPOSE: To evaluate an intratumoral polymer implant for sustained delivery of 5-fluorouracil (5-FU) in a mouse tumor model. METHODS AND MATERIALS: 5-FU was incorporated into a polyanhydride-based polymer, bis(p-carboxyphenoxy)propane sebacic acid (CPP:SA) and implanted in RIF-1 mouse fibrosarcoma growing s.c. The effectiveness of treatment was evaluated by tumor growth delay. External beam radiation was 60Co gamma rays, and the source of interstitial radiation was implanted 125I seeds. A second drug, cis-diamminedichloroplatinum (cis-DDP), was administered by intraperitoneal injection or by osmotic pump. RESULTS: For drug/polymer implant alone, the tumor growth delay was proportional to the amount of drug in the implant. The 5-FU polymer implant was most effective when combined with cis-DDP or with acute or fractionated radiation, and in some cases, the effects of combined treatments were greater than additive. The most effective combination was intratumoral 5-FU and low-dose-rate radiation delivered from an interstitial radiation source. CONCLUSION: Results indicate that 5-FU can be effectively delivered by polymer implant and that this mode of delivery is particularly appropriate for combined treatments.

Animals↗
PubMed2000

Biomaterials in drug delivery and tissue engineering: one laboratory's experience.

This Account reviews our laboratory's research in biomaterials. In one area, drug delivery, we discuss the development of materials that are capable of releasing macromolecules such as proteins and peptides, intelligent delivery systems based on magnetism or microchip technology, new degradable materials such as polyanhydrides, and noninvasive approaches for delivering molecules through the skin and lungs. A second area, tissue engineering, is also discussed. New polymer systems for creating cartilage, blood vessels, nerves, and other tissues are examined.

Animals↗
PubMedDate not supplied

Dextran retention in the rat brain following release from a polymer implant.

Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran).

Animals↗
PubMed1997

Implantable biodegradable polymers for IUdR radiosensitization of experimental human malignant glioma.

PURPOSE: The potential of halogenated pyrimidines for the radiosensitization of human malignant gliomas remains unrealized. To assess the role of local delivery for radiosensitization, we tested a synthetic, implantable biodegradable polymer for the controlled release of 5-iodo-2'-deoxyuridine (IUdR) both in vitro and in vivo and the resultant radiosensitization of human malignant glioma xenografts in vivo. MATERIALS AND METHODS: In vitro: To measure release, increasing (10%, 30%, 50%) proportions (weight/weight) of IUdR in the polyanhydride [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebacic acid (SA) (PCPP : SA ratio 20:80)] polymer discs were incubated (1 ml phosphate-buffered saline, 37 degrees C). The supernatant fractions were serially assayed using high performance liquid chromatography. To measure modulation of release, polymer discs were co-loaded with 20 microCi 5-125-iodo-2'-deoxyuridine (125-IUdR) and increasing (10%, 30%, or 50%) proportions of D-glucose. To test radiosensitization, cells (U251 human malignant glioma) were sequentially exposed to increasing (0 or 10 microM) concentrations of IUdR and increasing (0, 2.5, 5.0, or 10 Gy) doses of acute radiation. In vivo. To measure release, PCPP : SA polymer discs having 200 microCi 125-IUdR were surgically placed in U251 xenografts (0.1-0.2 cc) growing in the flanks of nude mice. The flanks were reproducibly positioned over a collimated scintillation detector and counted. To measure radiosensitization, PCPP : SA polymer discs having 0% (empty) or 50% IUdR were placed in the tumor or contralateral flank. After five days, the tumors were acutely irradiated (500 cGy x 2 daily fractions). RESULTS: In vitro: Intact IUdR was released from the PCPP : SA polymer discs in proportion to the percentage loading. After 4 days the cumulative percentages of loaded IUdR that were released were 43.7 +/- 0.1, 70.0 +/- 0.2, and 90.2 +/- 0.2 (p < 0.001 ANOVA) for the 10, 30, and 50% loadings. With 0, 10, 30, or 50% D-glucose co-loading, the cumulative release of 125-IUdR from PCPP : SA polymers was 21, 70, 92, or 97% (p < 0.001), respectively, measured 26 days after incubation. IUdR radiosensitized U251 cells in vitro. Cell survival (log10) was -2.02 +/- 0.02 and -3.68 +/- 0.11 (p < 0.001) after the 10 Gy treatment and no (control) or 10 microM IUdR exposures, respectively. In vivo: 125-IUdR Release: The average counts (log10 cpm +/- SEM) (hours after implant) were 5.2 +/- 0.05 (0.5), 4.3 +/- 0.07 (17), 3.9 +/- 0.08 (64), and 2.8 +/- 0.06 (284). Radiosensitization: After intratumoral implantation of empty polymer or intratumoral 50% IUdR polymer, or implantation of 50% IUdR polymers contralateral to tumors the average growth delays of tumors to 4 times the initial volumes were 15.4 +/- 1.8, 20.1 + 0.1, and 20.3 + 3.6 (mean + SEM) days, respectively (p = 0.488 one-way ANOVA). After empty polymer and radiation treatments, no tumors regressed and the growth delay was 31.1 + 2.1 (p = 0.046 vs. empty polymer alone) days. After implantation of 50% IUdR polymers either contralateral to the tumors or inside the tumors, followed by radiation, tumors regressed; growth delays to return to the initial average volumes of 14.0 + 3.6 or 24.2 + 0.2 (p < 0.01) days, respectively. CONCLUSIONS: Synthetic, implantable biodegradable polymers hold promise for the controlled release and local delivery of IUdR for radiosensitization of gliomas.

Animals↗
PubMed1998

Influence of surface properties at biodegradable microsphere surfaces: effects on plasma protein adsorption and phagocytosis.

OBJECTIVE: The objective of this work was to determine plasma protein adsorption and macrophage phagocytosis of biodegradable polyanhydride, polylactic acid and polylactic-co-glycolic acid microspheres prepared by both spray-drying and solvent evaporation techniques. METHODS: Microspheres were characterized by scanning electron microscopy (SEM), confocal laser microscopy, particle size distribution and zeta (zeta) potential determination. Plasma protein adsorption onto the microspheres was determined using a fluoroaldehyde reagent. Phagocytosis was evaluated by incubating microspheres containing the angiotensin II antagonist, L-158,809, with the macrophages in the presence or absence of the phagocytosis inhibitor cythochalasin D. The extent of phagocytosis was established by fluorescence determination of L-158,809 and by optical microscopy. The effect of amphiphilic poly(ethylene glycol) (PEG) derivatives on phagocytosis was determined using PEG-distearate incorporated into the microspheres. RESULTS: The average diameter of the microspheres, which depended on the polymer and the initial formulation, ranged from 0.9 to 3.2 micrometers. Zeta potential studies showed strong negative values irrespective of the polymer used for the spray-dried formulations. The zeta potential was masked by the incorporation of PEG 400- or PEG 1,400-distearate in the formulation. Confocal laser microscopy showed a homogenous dispersion of PEG (measured as PEG-fluorescein) in the microspheres. Protein adsorption was not observed for any of the microsphere formulations following incubation with bovine serum. Incubation of microspheres with murine macrophages showed that PEG-distearate inhibited phagocytosis at appropriate levels (0.1% w/w). Higher levels > 1% w/w of PEG-distearate) resulted in enhanced association with macrophages, despite the presence of the phagocytosis inhibitor cytochalasin D, indicating fusion between the microspheres and the plasma membrane. CONCLUSIONS: These results demonstrate that spray-dried PEG-containing microspheres can be manufactured and that an appropriate concentration of this excipient in microspheres results in decreased phagocytosis.

Adsorption↗
PubMed2002

Polymer delivery of camptothecin against 9L gliosarcoma: release, distribution, and efficacy.

Camptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro; unfortunately, systemic toxicity has limited its in vivo efficacy. This is the first study to investigate the release, biodistribution, and efficacy of camptothecin from a biodegradable polyanhydride polymer. Tritiated camptothecin was incorporated into biodegradable polymers that were implanted intracranially in 16 male Fischer 344 rats and the animals were followed up to 21 days post-implant. A concentration of 11-45 microg of camptothecin-sodium/mg brain tissue was within a 3 mm radius of the polymer disc, with levels of 0.1 microg at the outermost margin of the rat brain, 7 mm from the site of implantation. These tissue concentrations are within the therapeutic ranges for human and rat glioma lines tested against camptothecin-sodium in vitro. The in vivo efficacy of camptothecin-sodium was evaluated with male Fischer 344 rats implanted intracranially with 9L gliosarcoma and compared with the efficacy of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The animals were divided into four groups. Group 1 (control) had a median survival of 17 days. Group 2 (3.8% BCNU polymer) had a median survival of 23 days (P = 0.006). Group 3 (20% camptothecin polymer) had a median survival of 25 days (P = 0.023). Group 4 (50% camptothecin polymer) had a median survival of 69 days (P < 0.001). Drug loadings of 20% and 50% camptothecin released intact camptothecin for up to 1000 h in vitro. We conclude that the biodegradable polymer p(CPP: SA) releases camptothecin-sodium, produces tumoricidal tissue levels, results in little or no systemic toxicity, and prolongs survival in a rat glioma model.

Animals↗