Hepatic clearance of arterially infused ferromagnetic particles.

OBJECTIVE: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to determine if such particles are cleared from the liver. METHOD: A lobe of normal liver in three pigs was arterially embolized with 300 mg of gamma-Fe2O3 particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated microspheres (32 microm) suspended in 1% tween-water. Samples of liver and blood were obtained before infusion, and at 60 min and 28 days after arterial infusion. At 28 days, samples of lung and other abdominal viscera were also obtained. The tissue samples were chemically analysed for iron content, and submitted to histopathological examination. RESULTS: There was no significant reduction in the hepatic iron concentration in either treatment group 28 days after infusion. Both types of particles illicited an immunogenic response and were extensively phagocytosed in the liver. The particle/lipiodol suspension caused extensive necrosis of liver, while the microsphere/tween-water suspension was well tolerated. Small amounts of both types of ferromagnetic particles embolized in the lungs, but there was no evidence of embolization into other organs. There were no haematological or biochemical changes and all subjects experienced uneventful 28-day survivals. CONCLUSION: This study has shown that, although arterially infused ferromagnetic particles were extensively phagocytosed, there was no significant hepatic clearance 28 days after infusion. It also determined that the suspension of 150 nm ferromagnetic particles in lipiodol was too vaso-occlusive for use in hepatic tissue. However, the suspension of 32 microm microspheres containing ferromagnetic particles in tween-water was safe and well tolerated.

Magnetically mediated hyperthermia: current status and future directions.

The use of hyperthermia in the treatment of cancers is appealing because, as a physical therapy, hyperthermia would have far fewer restrictive side effects than chemotherapy and radiotherapy, and it could be used in combination with these therapies. However, the currently available modalities of hyperthermia are often limited by their inability to selectively target tumour tissue and, hence, they carry a high risk of collateral organ damage or they deposit heat in a very localized manner which can result in under-treatment of a tumour. Magnetically mediated hyperthermia (MMH) has the potential to address these shortcomings. MMH consists of the localization of magnetic particles or seeds within tumour tissue followed by exposure to an externally applied alternating magnetic field to cause them to heat. Since this concept was introduced (over 40 years ago), MMH has evolved into four general sub-classes: arterial embolization hyperthermia (AEH), direct injection hyperthermia (DIH), intracellular hyperthermia (IH) and interstitial implant hyperthermia (IIH). It is the purpose of this article to review these four sub-classes in terms of experimental or clinical results, advantages, limitations and current status.

Treatment of experimental rabbit liver tumours by selectively targeted hyperthermia.

Experimental rabbit liver tumours were preferentially heated to therapeutic temperatures without compromising the surrounding normal hepatic parenchyma. This was achieved by the use of hepatic arterially infused ferromagnetic microspheres that heat as a result of magnetic hysteresis loss when exposed to an alternating magnetic field. Treatment sessions involving a single 20-min exposure to the alternating field resulted in total suppression of tumour growth at 14 days compared to controls, in which tumour sizes increased dramatically over the same period. Histopathological examination of treated tumour sections showed total tumour destruction in some cases. Separate animal groups used to control for the effects of the embolized microspheres alone and for the effect of the applied magnetic field yielded similar tumour growth responses to a control group with no intervention whatsoever. The achievement of positive temperature differentials between tumour and normal liver and the consequent therapeutic responses encourages further development of this technology for the treatment of liver cancer in humans.

The effect of tumour size on ferromagnetic embolization hyperthermia in a rabbit liver tumour model.

OBJECTIVE: Ferromagnetic Embolization Hyperthermia (FEH) consists of arterially embolizing tumours with ferromagnetic particles to cause hysteretic heating upon subsequent exposure to an alternating magnetic field. The objective was to determine the effect of tumour size during FEH using a rabbit liver tumour model. METHOD: Thirty-three rabbits containing implanted hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Following hysteretic heating, tumour and normal hepatic tissues were chemically analysed for iron content. Tumours were classed as small if their mass was less than the median mass for the whole group of subjects (2.1 g), and as large if their mass was greater than or equal to the median. To control for variability in tumour iron concentration, 13 small tumours were matched to 13 large tumours by iron concentration, and their heating characteristics compared. RESULTS: The heating rate in large tumours (median = 5.0 degrees C/min) was significantly greater than that in the matched small tumours (median = 2.8 degrees C/min), p = 0.006. Regression analysis determined that the slope of the heating rate vs iron concentration curve for large tumours was 1.5 times greater than that for the matched small tumours, p < 0.001. After cessation of heating in large tumours, there was continued heat dissipation into surrounding tissues, which led to anomalous temperature increases. There was an inverse linear relationship between tumour size and tumour iron concentration for a given dose of particles. CONCLUSION: For a given tumour iron concentration, larger tumours heat at a greater rate than small tumours, due to the poorer tissue cooling and better heat conduction in the necrotic regions of large tumours. This warrants further investigation as this finding could confer a significant advantage on FEH over other hyperthermic modalities in the treatment of hepatic malignancies.

Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume.

OBJECTIVE: To determine the effect of selective internal radiation therapy (SIRT) and hepatic arterial chemotherapy (HAC) on normal liver volume and spleen volume in patients receiving these treatments for advanced liver cancer. METHODS: In a phase III clinical trial to assess the benefit of SIRT over HAC one group of patients received SIRT + HAC while a second group received HAC only. All patients in this trial who had abdominal CT scans available before treatment, and at 3, 6, and 12 months after treatment were evaluated. Changes in normal hepatic parenchyma (NHP) volume, portal vein diameter and spleen volume were calculated for each patient and analysed for significant trends. RESULTS: The mean NHP volume decreased by 17% (P = 0.001) 12 months after treatment among patients receiving SIRT + HAC (N = 22), while the mean NHP volume among patients treated with HAC only (N = 15) was unchanged at 12 months. The mean portal vein diameter increased by 9% in both treatment groups, P = 0.048 and P < 0.001, respectively. The mean spleen volume increased by 48% (P < 0.001) and 26% (P = 0.001), respectively, in the two groups 12 months after treatment started. There was no clinical evidence of hepatic failure, portal hypertension or splenic dysfunction in any of the patients. CONCLUSIONS: Treatment of patients with SIRT + HAC causes contraction of the normal hepatic parenchyma, while treatment with HAC alone has no significant effect. Treatment with either SIRT + HAC or HAC alone causes a significant increase in portal vein diameter and spleen volume by 12 months after treatment. The increase in spleen volume and portal vein size is likely to be due to portal hypertension resulting from scarring within the liver as a result of chemical and radiation hepatitis.

Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model.

BACKGROUND AND OBJECTIVES: Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS: Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS: The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS: Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.

Status of hyperthermia in the treatment of advanced liver cancer.

The vast majority of patients with malignant liver tumors have inoperable disease. These patients must rely on chemotherapy, radiotherapy, and various locoregional treatments. Although these treatments have demonstrated encouraging response rates, symptom palliation and occasional down staging of tumors, their impact on survival is minor. As a result there has been renewed interest in hyperthermia as a treatment option. This study reviews the current modalities of hyperthermia in terms of clinical results, side effects, limitations, and therapeutic standing.

Can current models explain the lack of liver complications in Y-90 microsphere therapy?

Normal liver complications have not been observed in Y-90 microsphere therapy of hepatic tumors [selective internal radiation (SIR)], despite clinical studies reporting estimated absorbed doses to normal liver between 100 and 150 Gy. The purpose of the study was to see whether predictions of normal tissue complication probability (NTCP) models for liver based on clinical data from external beam therapy are consistent with clinical results of SIR. Liver NTCP was calculated using a parallel architecture model and normal liver dose-volume histograms that have been proposed for SIR. A parallel model including internal functional subunit structure is also proposed. Dose rate effects are incorporated. A criterion for comparing model calculations with clinical data is presented. For the parallel architecture model, the predicted NTCP is sensitive to the dose distribution in normal liver and to the model parameters, particularly the repair time. With reasonable assumptions about the microsphere distribution, the parallel model with parameters deduced from external beam therapy outcome analysis is consistent with the observed lack of liver complications. Inclusion of FSU structure widens the range of assumptions under which consistency is found. The parallel model can be consistent with the clinically observed lack of liver complications in SIR. More information about the activity distribution and the radiobiology of normal liver under conditions typical of microsphere therapy should be sought.

Nurses screening for skin cancer: an observation study.

Skin cancer rates in Australia are the highest in the world and it is an important cause of mortality and morbidity. Screening is a method of control for skin cancer/melanoma through early diagnosis and prompt referral and treatment. To date, there have been no controlled trials evaluating the impact of screening on morbidity and mortality, and hence insufficient evidence to recommend for or against routine screening for skin cancer/melanoma by primary care providers. Australian health authorities have called for studies that investigate the viability of using trained observers apart from medical practitioners--such as nurses, pharmacists and physiotherapists--in opportunistic screening for skin cancer in populations that have a high prevalence of these skin cancers, largely on the basis of cost arguments. We conducted a double blind observation screening study comparing the performance of nurses to those plastic surgeons participating in a skin cancer screening program. The role of the nurse in this program was not to diagnose skin cancer, but to not miss lesions that required further specialist examination. Measurements were recorded for 256 screenees. Plastic surgeons issued 77 (30%) individual referrals for lesions suspicious of being skin cancer. Nurse observations noted 73 (95%) of these 77 cases. The case for the pre-screening of large populations for skin/cancer by trained nurses warrants further attention.

The use of targeted and non-targeted advertising to enrich skin cancer screening samples.

The purpose of this study was to determine whether the risk factor profile of persons attending skin cancer screening clinics could be enriched by appropriate advertising prior to the screening events. Eleven screening clinics were held in eight rural and three suburban communities. Matched communities were randomly assigned to either a target or non-target condition. Targeted communities received an advertisement designed to attract high-risk individuals. The advertisement listed a number of risk factors and encouraged readers with one or more of the listed risk factors to attend the screening. Non-targeted communities received a general advertisement requesting individuals who felt they were at risk of skin cancer to attend the clinic. Risk factor profiles of all participants were measured on the factors listed in the targeted advertisement. The risk factor profiles of screenees and the referral rates for skin lesions requiring attention were significantly higher in the targeted communities than in the non-targeted communities. Lesions suspicious of malignant melanoma or Hutchinson's melanotic freckle also were higher, but not statistically significant, in the targeted communities. Population samples attending community-based skin cancer screening clinics can be enriched by appropriate targeted advertising prior to the screening events. This has important implications for determining the potential cost-effectiveness of population screening programmes.

Immunohistochemical characterisation of immunological changes at the tumour site after chemo-immunotherapy with doxorubicin, interleukin-2 and interferon-gamma.

Chemo-immunotherapy for the treatment of cancer, whilst promising from a preclinical and clinical perspective, remains limited by a lack of clear understanding of the in vivo antitumour mechanisms of this multi modality strategy. There is now strong evidence that systemic immunological parameters do not correlate with therapeutic activity. In contrast, information on therapy related immunological change at the tumour site is scarce. Having previously demonstrated that the therapeutic activity of doxorubicin chemotherapy can be significantly augmented by the co-administration of two cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), the objective of the present study was to investigate the mechanism of action of this enhanced therapeutic activity by characterising the effect of single, double and triple agent therapy upon local tumour immune parameters. Twenty-four hours after the administration of treatment to WAG rats bearing solid tumour implants of a colonic adenocarcinoma, the extent of tumour infiltration in response to the therapy was assessed in haematoxylin and eosin stained tumour sections. Treatment with doxorubicin/IL-2/IFN-gamma or IL-2/IFN-gamma was associated with a marked augmentation of the size of the tumour infiltrate (P < 0.001), as compared to untreated tumours or to those treated with any other single or double agent combination. Phenotypic evaluation of the tumour infiltrate using immunoperoxidase stained tumour sections revealed that a considerable proportion of the infiltrating cells were T cells and macrophages, whilst B cells were not detected in significant numbers. Although this phenotypic profile was not qualitatively influenced by therapy, marked quantitative differences were observed. Most notably, tumours treated with either doxorubicin/IL-2/IFN-gamma or IL-2/IFN-gamma exhibited a significant increase in the numbers of CD25+ infiltrating cells (P < 0.001). These changes in the tumour immunological response closely paralleled the therapeutic responses described previously. Thus, the enhanced therapeutic activity of the triple agent regimen may result from a profound augmentation of the size of the tumour infiltrate, together with a similar increase in the numbers of activated infiltrating cells. This study supports the concept that the immune response within the tumour is the appropriate site for investigations into the immunological antitumour mechanisms of immunotherapy and chemo-immunotherapy.

Research note: the Lions Cancer Institute and the Western Australian Society of Plastic Surgeons skin cancer screening programme.

BACKGROUND: The Lions Cancer Institute, Perth, and the Western Australian Society of Plastic Surgeons have been investigating the feasibility of community based skin cancer screening. Members of the community responded to newspaper advertisements to attend free skin cancer screening events. This report presents preliminary results obtained from the methods development programme. METHODS: Seventeen screening clinics were conducted in Perth (4) and country towns (14) in Western Australia between January 1991 and October 1993. The participants were interviewed and given promotional literature and their personal profiles were determined. A total body skin examination was performed by a specialist plastic surgeon and any suspicious lesions were recorded and, if necessary, recommendations for further treatment was documented. RESULTS: The number of individuals screened was 3397. Of these, 572 patients were referred to general practitioners for further medical attention of suspicious lesions, 79 patients were clinically diagnosed as having suspicious pigmented skin lesions (13.8% of total lesions and 2.3% of total sample screened). Of these, 53 individual patient pathology reports were obtained. Four invasive malignant melanomas and two in situ melanomas arising in Hutchinson's melanotic freckles were detected. CONCLUSIONS: Debates concerning the efficacy of screening for skin cancer have recently received great attention from many medical disciplines. However, as yet the effectiveness of population based skin cancer screening programmes have not been adequately evaluated with randomized controlled studies. The study reported here provides some findings that may be used to enhance future screening studies.

Retroperitoneal schwannoma: a case series and review.

Schwannomas account for only a small percentage of retroperitoneal tumours. Presentation is typically varied and non-specific and pre-operative diagnosis is difficult. Herein are described five cases of retroperitoneal schwannoma. Presentation was varied, ranging from abdominal pain, abdominal mass, obstructed labour or an incidental finding. All patients had either an abdominal computed tomography scan and/or ultrasound performed. Pre-operative biopsy either by fine needle aspiration (in one patient) or core biopsy in two patients was unhelpful. In four patients with smaller tumours, complete excision was possible with no apparent long-term morbidity and no clinical evidence of recurrent tumour with follow up from 3.5 months to 11 years. For the largest tumour, complete surgical excision was not attempted as it would have entailed significant morbidity.

Adjuvant internal radiation therapy in a model of colorectal cancer-derived hepatic metastases.

Selective internal radiation therapy (SIR therapy) is a technique whereby metastatic liver cancer is irradiated by embolising microspheres containing the radionuclide yttrium-90 into the hepatic arterial circulation. To date this technique has not been used as an adjuvant therapy, but rather to treat established metastases in the liver. This study evaluated the use of two intrahepatic radiation doses delivered on radioactive microspheres for the treatment of small, growing micrometastases. Three groups of five rats were each inoculated with tumour spheroids into the portal vein. The resultant liver micrometastases were treated with either 10 or 20 MBq of yttrium-90 microspheres or a sham dose of non-radioactive microspheres injected into the portal vein 2 days following tumour inoculation. The livers of each animal were examined for the presence of metastases after a further 21 days and liver function tests were performed. At the time of sacrifice there was no obvious normal liver damage in any of the rats treated with microspheres. The livers of the sham-treated animals contained extensive signs of tumour deposition. A mean of 34 tumours were taken from the livers of each of the sham-treated animals, whereas only a single tumour was found in one animal treated with 10 MBq of yttrium and eight small tumours from two animals treated with 20 MBq. Liver function tests demonstrated a significant short-term increase in alkaline phosphatase levels in the radiation-treated animals compared with shams, but there were no other indications of any effects on liver function. These results indicate a potential role for SIR therapy in an adjuvant setting with colorectal cancer.

The solution conformation of a trisdecanucleotide containing the consensus binding site of the dnaA initiation protein.

The solution structure of a trisdecanucleotide, d(CCTGTGGATAACA).d(TGTTATCCACAGG) containing the consensus binding site of the dnaA initiation protein has been determined by two-dimensional NMR techniques and restrained molecular dynamics calculations. Interproton distances were obtained by an iterative complete relaxation matrix algorithm, MARDIGRAS. During molecular dynamics runs, the backbone was restricted with the assistance of experimentally derived distance constraints. A family of refined structures with small pairwise root-mean-square deviation values (approximately 0.08 nm) was obtained. All but one of the pyrimidines were found to adopt the C1'-exo conformation while the purines were found to adopt the C2'-endo or C1'-exo conformation. The six-membered rings of the purines were found to stack over the six-membered rings of the pyrimidines while there is virtually no overlap of the pyrimidines over the purines. 5'-purine-purine-3' and 5'-pyrimidine-pyrimidine-3' stacking resembles the observed stacking of these bases in other NMR and X-ray structures of oligonucleotides. The final refined structure exhibited a small curvature and was slightly longer than canonical B-DNA. The variation of twist angle, proposed as a recognition element for proteins, exhibited symmetry about the centre of the consensus binding site.

A comparative study of the anticancer efficacy of doxorubicin carrying microspheres and liposomes using a rat liver tumour model.

Due to low efficacy of chemotherapy in the treatment of liver cancer, several methods of drug targeting have been investigated. Liposomes designed to carry cytotoxic drugs to the liver are currently under clinical evaluation. While experimental evidence shows promise, this method of drug delivery has several disadvantages that include short shelf life and poor drug delivery into tumour tissue. An alternative strategy for targeted drug delivery involving use of ion exchange microspheres may overcome these limitations while still reducing systemic toxicity and maintaining therapeutic efficacy. The purpose of this study was to determine the relative antitumour efficacy of these two drugs carrying systems in the treatment of liver cancer. Compared to controls, DOX treatment with free drug, liposomes or microspheres significantly reduced tumour growth by 56% (P < 0.001), 51% (P < 0.01) and 79% (P < 0.001) respectively. Furthermore, the DOX-microsphere treatment was significantly better than either of the other DOX treatments (53%, P < 0.05) or the sham-microsphere treated group (64%, P < 0.05). Thus, drug microspheres can increase the anti-tumour efficacy compared to either free or liposomal drug while simultaneously reducing systemic toxicity.

Prevention of myelosuppression does not improve the therapeutic efficacy of chemo-immunotherapy.

This study was designed to investigate whether the prevention of doxorubicin (DOX) induced myelosuppression could further improve the therapeutic efficacy of chemoimmunotherapy with DOX, interleukin-2 (IL-2) and interferon gamma (IFN-gamma). The antitumour activity of systemic IL-2/IFN-gamma immunotherapy in combination with DOX administered either systemically, regionally or on ion-exchange microspheres, was assessed in WAG rats bearing hind limb solid colonic adenocarcinoma implants. Whilst the use of microspheres to transport DOX clearly avoided the myelosuppression, systemic and renal toxicity associated with the use of free DOX, it did not provide any therapeutic advantage over chemo-immunotherapy with free systemic or regional drug.

Improved efficacy of doxorubicin by simultaneous treatment with interferon-gamma and interleukin-2.

Doxorubicin (DOX) is a potent anticancer agent active against a wide range of human neoplasms, yet, as is characteristic of most chemotherapeutics, the treatment of cancer with DOX alone has met with only limited success. This study was designed to investigate the possibility that the therapeutic potential of DOX could be enhanced by combination with one or more biological response modifiers. Segments (1mm3) of a transplantable colonic adenocarcinoma were implanted into the hind limbs of male WAG rats (200-250g). Serial tumour measurements were taken 3 x weekly throughout the 4 week experimental period by measuring the longest and perpendicular lengths with calibrated calipers. All drug administration was via a chronic indwelling jugular catheter, commencing 12 days after tumour implant, with control animals receiving physiological saline. Treatment of animals with DOX (4.5mg/kg as a 15 minute i.v. infusion), interferon gamma (IFN-gamma) (5 x 10(5) U/kg/day bolus i.v. for 5 days) or interleukin-2 (IL-2) (1 x 10(5)U/rat/day continuous i.v. infusion for 5 days) retarded tumour growth by approximately 30% by the completion of the study period (P < 0.001). The combined administration of IFN-gamma with DOX did not significantly alter the antitumour activity of either DOX or IFN-gamma. Concurrent administration of IL-2 with DOX also showed this treatment to have no therapeutic activity over that achievable with either agent alone. However, treatment of animals with IL-2, IFN-gamma and DOX resulted in a significant increase in tumour growth inhibition compared to DOX with either single cytokine (P < 0.001) and this was achieved without any apparent increases in the gross toxicity of DOX.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro and in vivo responses of doxorubicin ion exchange microspheres to hyperthermia.

The utility of microspheres as targeted drug delivery agents is addressed with reference to using heat during formulation and to administration in combination with hyperthermia. It was demonstrated that rate of loading of the drug doxorubicin onto resin microspheres is enhanced under conditions of elevated temperature but this was shown to increase the incidence of microsphere aggregation. Total amount of drug loaded was related to time rather than temperature such that low temperature loading for up to 24 h produced optimum quality injectates. However, release of doxorubicin from microspheres was significantly increased during elevations of temperature to 43 degrees C. Thus, during hyperthermia doxorubicin release can be increased to provide periods of high drug availability targeted to tumour tissue for concomitant thermochemotherapy with microspheres. The therapeutic benefit derived from this combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the exteriorized liver at 43 degrees C for 30 min, while chemotherapy was administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into each tumour. Both hyperthermia and chemotherapy alone significantly reduced the size of tumours 10 days following treatment (p less than 0.01). However, in animals treated with both modalities, the size of tumours was significantly less than either treatment alone (p less than 0.05). These results provide a strong rationale for combining hyperthermia with targeted chemotherapy using microspheres.

Evaluation of ion-exchange microspheres as carriers for the anticancer drug doxorubicin: in-vitro studies.

A comparison study of doxorubicin loading, release characteristics and stability within sodium and hydrogen forms of ion-exchange resin microspheres has been performed. It was demonstrated that resins in the Na+ form, although having lower drug loading capacity, showed similar release profiles to resins in the H+ form but still maintain all the drug activity. Resins in the H+ form, despite having high drug loading capacity, caused drug degradation within microspheres due to their strong acidic nature. Therefore, in comparison with the H+ form, resins in the Na+ form can be considered as better carriers for doxorubicin in terms of sustaining the release of drug and maintaining drug activity. Other factors such as the degree of resin cross-linkage and drug/resin mixing time have also been examined in relation to drug loading and release characteristics. Overall, this study demonstrated the significance of the characteristics of matrix materials and their influence on the drug activity and microsphere performance in-vitro.