[Show abstract][Hide abstract] ABSTRACT: Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process.
Polymeric nanoparticles were prepared by nanoprecipitation of Eudragit® RS 100 in presence and in absence of glycofurol. The photosensitizer temoporfin has been encapsulated into these carrier devices. Process parameters were optimized by means of a Design of Experiments approach and nanoparticles with optimal characteristics were manufactured by using microreactor technology. The efficacy was determined by means of cell culture models in A-253 cells.
Physicochemical properties of nanoparticles achieved by nanoprecipitation from ethanolic solutions were superior to those obtained from a method based upon glycofurol. Nanoencapsulation of temoporfin into the matrix significantly reduced toxicity of this compound, while the efficacy was maintained. The release profiles assured a sustained release at the site of action. Finally, the transfer to continuous flow technology was achieved.
By adjusting all process parameters, a potent formulation for application in the GI tract was obtained. The essential steps of process development and scale-up were part of this formulation development.
Pharmaceutical Research 11/2014; 32(5). DOI:10.1007/s11095-014-1569-y · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives The present in vitro study investigates the antimicrobial photodynamic efficiency of the photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC) incorporated in liposomes (LIP) and highly flexible invasomes (INV) on the endodontopathogenic species Enterococcus faecalis in infected dental root canals. Materials and methods A total of 48 root canals were prepared mechanically to file size ISO 50 and inoculated with E. faecalis for 48 h. In the test groups, the infected root canals were subjected to aPDT with either mTHPC linked to LIP or INV. The controls were either incubated with 1 % chlorohexidine gel (CHX, positive control) or root canals were irrigated with normal saline (NaCl, negative control). After treatment all canals were mechanically enlarged (ISO 50-110), and the debris of each filing process was subjected to bacterial culture analysis. Results Both mTHPC formulations showed a significant antimicrobial effect. A bacterial reduction by up to 3.6 log-steps was ascertained for INV directly at the root canal wall. aPDT using INV (ISO 60) was more effective than CHX, which caused a decrease in only 1.2 log-steps. It was found that both liposomal mTHPC formulations were capable to suppress E. faecalis inside the dentinal tubules up to 300 μm. Conclusions The results show that mTHPC linked to LIP and INV is capable of efficiently reducing E. faecalis in dental root canals. Clinical relevance As evidenced, E. faecalis is resistant to several conventional antibacterial treatment measures. In this context, photodynamic treatment with mTHPC delivered by INV is superior to temporary dressing with 1 % CHX gel applied for 24 h.
[Show abstract][Hide abstract] ABSTRACT: In a previous publication we showed that mTHPC-PDT (Foscan®-PDT) is an effective treatment of basal cell carcinomas (BCCs) in "difficult to treat" locations and presented optimized treatment parameters to reduce costs and side effects. Now we present long-term results of the same study population.
Following PDT of a total of 460 BCCs in 117 subjects, the patients/lesions were followed-up for a mean duration of 42 (range: 2-72) months. Two patients dropped out of follow-up; 13 patients died of unrelated causes. Recurrences were treated either by repeated PDT or other established methods.
The sustained clearance rate was 93.7% and the overall treatment success rate was 90.7%. Kaplan-Meier analysis revealed an estimated recurrence free fraction of patients at 5 years of 95.1%, 92.4%, 85.1%, and 74.0% for the four different photosensitizer dose groups (0.06-0.15, 0.05, 0.04, and 0.03 mg/kg). High-risk lesions (recurrences, thickness >3 mm) recurred more often than low-risk ones, and recurrences mostly (>50%) occurred during the first year of follow-up.
Long-term outcomes of high-dose (0.06-0.15 mg/kg) and reduced-dose (0.05 mg/kg) Foscan®-PDT in "difficult to treat" BCCs compare favorably with other methods, even in high-risk lesions (recurrent and/or thick lesions). A recommended combination of treatment parameters for low-dose therapy seems to be: 0.05 mg/kg Foscan®, 24 hours drug-light interval (DLI), fluence ≥40 J/cm(2) . Prospective randomized studies are needed to look into low-dose mTHPC-PDT of BCCs in more detail and to directly compare it with other treatments.
Lasers in Surgery and Medicine 09/2012; 44(7):533-40. DOI:10.1002/lsm.22056 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria-targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin-loaded liposomes using an activated phospholipid containing N-hydroxylsuccinimide residue. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA- modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA- modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA- modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram-positive and Gram-negative bacterial cells.
Photochemistry and Photobiology 08/2011; 88(3):548-56. DOI:10.1111/j.1751-1097.2011.00983.x · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.
[Show abstract][Hide abstract] ABSTRACT: Objectives: The antimicrobial Photodynamic Therapy (aPDT) shows great potential in the treatment of oral infections. To increase the antimicrobial efficiency, Photosensitzers (PS) are related to special carrier-systems. Concerning this issue, the present In-vitro-Study focused on aPDT of Enterococcus faecalis, Streptococcus mutans and Porphyromonas gingivalis using the PS mTHPC bound to liposomes.
Methods: Each bacterium was anaerobically cultured in Schaedler fluid media for 24 h. The cells were pelleted by centrifugation, washed twice with PBS and resuspended in the same media to an A546nm of 0.3 (app. 108 cells/ml). The liposomal PS-formulation was added and concentrations of 10, 30 and 50 M mTHPC were established. Prior to any further treatment an incubation time of 15 min was insured. In group A) all samples were subjected to laser light (652 nm, 100 Jcm-2). In group B) none of the photosensitized samples did receive any irradiation (dark toxicity). In group C) the bacterial solutions without PS were illuminated by laser light (100 Jcm-2). The treated solutions of all groups were diluted (100-10-6) and plated on Schaedler agar. After anaerobe cultivation (4-6 days) the colony-forming-units (CFU/ml) were encountered. Results were statistically analyzed by Mann-Whitney-U-Test.
Results: E. faecalis and S. mutans were suppressed completely by aPDT using 50 M liposomal mTHPC. In the case of P. gingivalis, the same treatment led to a reduction of 5.3 log units. The PS did show only little dark toxicity on E. faecalis and P. gingivalis while S. mutans was reduced up to 2 log units after incubation with 50 M mTHPC. Irradiation of the non-sensitized bacterial solution by laser light did not have any significant impact on bacterial growth. Conclusion: The results indicate that aPDT using liposome bound mTHPC might be an alternative antibacterial strategy to suppress oral pathogens.
[Show abstract][Hide abstract] ABSTRACT: Enterococcus faecalis is frequently found in persistent endodontic infections. In this context, the antimicrobial photodynamic therapy (aPDT) could become a modern alternative to existing antibacterial treatment approaches. The aim of this study was to investigate the effect of aPDT on E. faecalis using the photosensitizer (PS) 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC) enriched in liposomes.
Enterococcus faecalis was cultivated in Schaedler submerged culture for 24 hours, then isolated and adjusted in PBS to 10(8) cells/ml. The bacterial suspension was pipetted into a black microtitration plate and incubated for 15 minutes in the dark with mTHPC in various concentrations (10, 30, and 50 µM). The photosensitized suspensions were subjected to laser light (652 nm) at a light fluence of 100 J cm(-2) (test group A). In addition, the suspension sensitized with 50 µM mTHPC was irradiated with 25, 50, and 75 J cm(-2) (test group B). The following controls were used: non-irradiated bacterial suspension in the absence of mTHPC (C); irradiated bacterial suspension in the absence of mTHPC (D); non-irradiated bacterial suspension incubated with mTHPC (E). Dilution series (10(0)-10(-6)) were made of all groups and applied on Schaedler agar. After anerobic cultivation (4 days), the colony-forming units (CFU/ml) were determined.
Enterococcus faecalis was suppressed completely after incubation with 50 µM mTHPC and illumination with 100 J cm(-2). Photodynamic treatment with 10 and 30 µM mTHPC caused reduction in CFU by 5.8 and 6.7 log-units. The application of an energy fluence <100 J cm(-2) resulted in a decline of antibacterial efficiency. Irradiation of the non-photosensitized solution showed no suppressing impact. Incubation of the PS without additional irradiation caused a maximal reduction in CFU by 1.5 log-units.
The results show that aPDT using the PS mTHPC incorporated in liposomes could be a new approach to adjuvant treatment of endodontic infections with E. faecalis.
Lasers in Surgery and Medicine 03/2011; 43(3):241-8. DOI:10.1002/lsm.21046 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: Enterococcus faecalis is frequently detected in persistent endodontic infections. The antimicrobial photodynamic therapy (aPDT) is a promising alternative to existing antibacterial treatments. The in-vitro study described was aimed at testing the antibacterial action of the mTHPC photosensitizer, enriched in liposomes, on E. faecalis.
MATERIALS AND METHODS: E. faecalis was cultivated in submerged Schaedler culture for 24 hours, subsequently isolated and set to an optical density of 0.3 in physiological saline solution. The bacterial suspension (190 l) was then pipetted into a black 96-well microplate and incubated with PS (10 l) in the dark for 15 min in different final concentrations (10, 30 und 50 M). The suspension, with photosensitizer added, was irradiated with the light of a diode laser (Ceralas PDT, 652nm, biolitec AG, Jena) at different energy densities. Control groups were: a) untreated bacterial suspension, b) bacterial suspension irradiated with laser light, and c) non-irradiated bacterial suspension with PS (dark toxicity). To enable counting of bacterial colonies, dilution series of all groups down to 10-6 were made. After anaerobic cultivation the colony-forming units (CFU/ml) were determined. This was followed by statistical analysis (Mann-Whitney U test, p<0.05). RESULTS: The procedure had a differentiated influence on bacterial growth. With a final PS concentration of 50 M (energy density 100 J/cm2), E. faecalis was completely eliminated. With final concentrations of 10 und 30 M (100 J/cm2), bacterial growth rates were found to decrease by 105 KBE/ml.
CONCLUSION: The results of the study have shown that this aPDT method is a potential adjuvant treatment procedure for endodontic infections with E. faecalis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to develop ethanol-containing (3.3-20%, w/v) liposomes loaded with temoporfin (mTHPC), which presents a highly hydrophobic photosensitizer with low percutaneous penetration, and to investigate their skin penetration enhancing effect. Characterization parameters of liposomes were measured by photon correlation spectroscopy, lamellarity was analyzed by cryo-electron microscopy and mTHPC-content in formulations was determined spectrofotometrically. In order to assess the stability of mTHPC-liposomes at 4 and 23 degrees C, at predetermined time intervals characterization parameters and mTHPC-content were measured. The in vitro skin penetration of mTHPC was investigated using human abdominal skin mounted in Franz cells. The results indicated that mTHPC-liposomes were of a small particle size, small polydispersity index, negative surface charge, unilamellar or oligolamellar, and of a spherical or oval shape. All liposomes were stable during 12 months' storage at 4 degrees C. Increasing the amount of ethanol in mTHPC-liposomes the skin deposition of mTHPC increased also. Liposomes without ethanol delivered the lowest amount of mTHPC into the skin, while liposomes containing 20% ethanol showed the highest penetration enhancement. In conclusion, mTHPC-liposomes containing 20% ethanol could be a promising tool for delivering temoporfin to the skin, which would be beneficial for the photodynamic therapy of cutaneous malignant or non-malignant diseases.
[Show abstract][Hide abstract] ABSTRACT: Objectives: Basal cell carcinomas (BCCs) are the most common skin cancers, and incidence rates are still rising. Photodynamic Therapy (PDT) with mTHPC (FoscanÂ®) has shown to be a promising alternative to other treatments with good cosmetic results. This study was performed to determine optimal treatment parameters for this indication. Methods: 117 patients with a total of 460 BCCs received mTHPC-PDT. The treatment parameters were varied as follows: FoscanÂ® dose 0.03 - 0.15 mg/kg, drug-light interval (DLI) 1 - 96 hours, total energy density 20 - 120 J/cm2. The clinical outcomes were assessed 8 weeks after PDT following WHO guidelines. Results: The rate of complete remissions (CR) was 96.7% and the general cosmetic outcome rated very good. In the largest subgroup (n=80) with low-dose mTHPC (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm2 total energy density), a CR rate of 100% was accomplished. Minor changes of the parameters (0.04 mg/kg mTHPC or 24 hours DLI) yielded similar results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06 - 0.15 mg/kg) and comprised pain and phototoxic reactions. 3 patients developed severe sunburns with subsequent scarring at the injection site following sunlight exposure 2-3 weeks after mTHPC administration. Conclusions: The data suggests that low-dose mTHPC-PDT is an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. The evaluation of long term results is still to be undertaken.
Proceedings of SPIE - The International Society for Optical Engineering 06/2009; 7380. DOI:10.1117/12.822063 · 0.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A previous study revealed that the invasome dispersion containing 3.3% (w/v) ethanol and 1% (w/v) of the terpene mixture (cineole:citral:d-limonene=45:45:10, v/v=standard mixture) could significantly enhance skin penetration of the highly hydrophobic photosensitizer temoporfin (mTHPC). Invasomes enhanced mTHPC-deposition in stratum corneum (SC) compared to liposomes without terpenes and conventional liposomes, and they were efficient in delivering mTHPC to deeper skin layers [J. Control. Release 127 (2008) 271-280]. The aim of this study was to develop new mTHPC-loaded invasomes in order to further enhance the drug penetration. The ratio between d-limonene, citral and cineole was varied in the standard terpene mixture and also single terpenes were used. As a result new mTHPC-loaded invasome dispersions were prepared, characterized and investigated for stability and in vitro penetration of mTHPC into abdominal human skin using Franz diffusion cells. Invasomes were of a small particle size (<150nm), high homogeneity (<0.3), mostly unilamellar and spherical, but also deformed vesicles were detected. Invasomes containing 1% (w/v) cineole provided the highest skin penetration enhancement of mTHPC, i.e. they provided high amounts of mTHPC in the SC and deeper skin layers, indicating that also incorporation of a single terpene into invasomes could provide efficient nanocarriers of mTHPC. These invasomes could be considered as a promising tool for delivering the photosensitizer mTHPC to the skin. However, in contrast to most invasomes, being effective nanocarriers of mTHPC, there were also formulations less effective than liposomes containing 3.3% (w/v) ethanol and one formulation was less efficient than conventional liposomes.
[Show abstract][Hide abstract] ABSTRACT: Basal cell carcinomas (BCCs) are the most common form of skin cancers with high and increasing incidence rates. Photodynamic therapy (PDT) with mTHPC (Foscan) has shown to be a promising treatment alternative with good cosmetic results. The current study was aimed to determine optimal treatment parameters for this indication.
mTHPC-PDT was performed in 117 patients with a total of 460 BCCs with diagnosis confirmed by scratch cytology. Treatment parameters were altered as follows: Foscan dose 0.03-0.15 mg/kg, drug-light interval (DLI) 1-96 hours, total energy density 20-120 J/cm(2). Outcomes were assessed 8 weeks post-PDT following WHO guidelines.
The overall rate of complete remissions (CR) was 96.7% and the cosmetic outcome was very good. In the largest subgroup (n=80) where low-dose Foscan was applied (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm(2) total energy density), a CR rate of 100% with a high and narrow 95% Confidence Interval of 0.955-1.000 was achieved. Smaller variations of the treatment parameters (i.e., reducing the photosensitizer dose to 0.04 mg/kg or shortening the DLI to 24 hours) yielded similarly good results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06-0.15 mg/kg) and comprised mostly pain and phototoxic reactions. Three patients developed severe sunburns with subsequent scarring at the injection site following bright sunlight exposure 15-19 days after photosensitizer administration.
The presented data suggest that mTHPC-PDT with the treatment parameters mentioned above seems to be an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. Long-term results are yet to be evaluated.
Lasers in Surgery and Medicine 07/2008; 40(5):300-11. DOI:10.1002/lsm.20632 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Temoporfin (mTHPC) is a highly hydrophobic second generation photosensitizer with low percutaneous penetration. In order to enhance its percutaneous penetration it was necessary to develop a mTHPC-loaded drug carrier system for enhanced skin delivery. mTHPC-loaded invasomes were developed, characterized and investigated for the in vitro percutaneous penetration of mTHPC into abdominal human skin using Franz diffusion cells. mTHPC-loaded invasomes were prepared using non-hydrogenated soybean lecithin (10% w/v), ethanol (3.3% w/v) and a mixture of terpenes (0.5 and 1% w/v). The invasomes obtained were of a sufficiently small particle size (<150 nm) and polydispersity index (<0.3). The particle size of invasomes increased following an increase in the amount of terpenes in the invasomes. All invasomes possessed a negative surface charge. The vesicles appeared to be unilamellar and oligolamellar, spherical and oval in shape. An interesting phenomenon was the finding that with increasing the amount of terpenes, the number of deformed vesicles in the dispersion increased. In vitro skin penetration data revealed that the invasome dispersion with 1% of the mixture of terpenes showed a significantly enhanced deposition (p<0.05) of the drug in the SC compared to liposomes without terpenes and the ethanolic solution.
[Show abstract][Hide abstract] ABSTRACT: Temoporfin (mTHPC) represents a very potent second-generation synthetic photosensitizer. It has shown to be effective in the photodynamic therapy of early or recurrent oral carcinomas, in the palliative treatment of refractory oral carcinomas and in the treatment of primary non-melanomatous tumours of the skin of the head and neck. Until now for all positive findings an intravenous application of the photosensitizer was mandatory. In the case of cutaneous malignant or non-malignant diseases a topical application of the drug onto the site of the disease followed by illumination, would be advantageous. Unfortunately, mTHPC is a highly hydrophobic drug with a low percutaneous absorption. The purpose of this experiment was to investigate the photodynamic efficacy of novel mTHPC-loaded invasomes after their topical application onto the skin of mice bearing the subcutaneously implanted human colorectal tumour HT29 followed by photoirradiation. Invasomes are vesicles containing in addition to phospholipids a mixture of terpenes (cineole, citral and d-limonene) or only one terpene (citral) and ethanol, as penetration enhancers. This was a pilot study since until now no data are available about the efficacy of mTHPC in the photodynamic therapy of HT29 tumours after its topical application. The aim of this experiment was to investigate whether a mTHPC-loaded invasome formulation can reduce tumour size by photodynamic therapy or at least to find a formulation slowing down tumour growth compared to the control group (mice without any treatment). The groups of mice treated with mTHPC-invasomes containing 1% of the terpene mixture prior to photoirradiation showed a significantly smaller (p<0.05) tumour increase compared to control groups (mice without any treatment and mice only photoirradiated).
Journal of Photochemistry and Photobiology B Biology 05/2008; 91(1):41-50. DOI:10.1016/j.jphotobiol.2008.01.009 · 2.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate the ability of meso-tetra(hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30 s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500 s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100 J/cm2) higher than with Fospeg (50 J/cm2). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration.
European Journal of Pharmaceutical Sciences 06/2006; 28(1-2):134-40. DOI:10.1016/j.ejps.2006.01.008 · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.
Photochemistry and Photobiology 11/2005; 81(6):1505-10. DOI:10.1562/2005-02-23-RA-448 · 2.27 Impact Factor