AbstractRecent preclinical and clinical testing of hypocrellin‐based photosensitizer SL052 for use in photodynamic therapy (PDT) of cancer has shown encouraging results. Further optimization of its formulation for delivery could considerably extend the therapeutic efficiency of this drug. A nanoformulation encapsulating SL052 into biodegradable polymer poly(lactic‐co‐glycolic acid) (PLGA) was developed using a single‐emulsion solvent evaporation technique and characterized in terms of particle size and loading of the photosensitizing agent. This nanoformulation, SL052‐PLGA‐nanoparticles (NPs), was compared with recently created nanoformulation based on polyvinylpyrrolidone (SL052‐PVP‐NPs) and standard liposomal SL052 preparation in terms of efficacy when used for PDT treatment of squamous cell carcinomas SCCVII growing subcutaneously in syngeneic mice. The therapeutic effect of PDT using these three different SL052 formulations was tested for both 1 and 4 h intervals between drug injection and tumor light exposure. The longer time interval produced higher tumor cure rates with all SL052 preparations. With both drug‐light intervals, PDT based on SL052‐PLGA‐NPs produced superior therapeutic benefit compared with the other two SL052 formulations.

01 Dec 2010·NanomedicineQ3 · MEDICINE

Water-Soluble and Biocompatible Sono/Photosensitizer Nanoparticles for Enhanced Cancer Therapy

Q3 · MEDICINE

Article

Author: Zou, Chunpu ; Chen, Jie ; Huang, Min ; Meng, Yongde ; Xing, James Z ; Swanson, Eric ; Yang, Xiaoyan ; Madiyalakan, Ragupathy ; Woo, Thomas

Aims: Most sono/photosensitizers of cancer sonodynamic/photodynamic therapy (SDT/PDT), such as hypocrellin SL052, are water-insoluble, therefore restricting their clinical applications. In this article, we present a water-soluble nanocarrier to load the SDT/PDT sensitizer SL052 with improved pharmacokinetics and therapeutic efficacy. Materials & methods: Nanoclusters of polyvinylpyrrolidones with SL052 formed water-soluble nanoparticles (SL052-NPs) while retaining the chemical structure of SL052. Results: The experimental results show that SL052-NPs improve the drug’s physicochemical properties and significantly enhance the efficacy of SL052 in terms of pharmacokinetics and cancer killing. Water-soluble SL052-NPs can be used to deliver the drug to deep cancer tissues. A potential benefit of SL052-NPs is that polyvinylpyrrolidones can help SL052 evade the reticuloendothelial system, thereby increasing circulation half-life and improving drug biodistribution. Conclusion: SL052-NPs greatly improved the physicochemical properties of SL052 without modifying its chemical structure, allowing for deep-site cancer drug delivery, imaging for diagnosis, and ultrasound or photocontrolled localized cancer therapy.

01 Jun 2010·Photodiagnosis and Photodynamic TherapyQ3 · MEDICINE

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate

Q3 · MEDICINE

Article

Author: Richard J. Owen ; Kevin Brown ; John Tulip ; Ronald B. Moore ; Thomas Woo ; Zhengwen Xiao ; Weiyang Liu

BACKGROUNDCurrent limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model.METHODSA lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment.RESULTS AND CONCLUSIONThirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Phase 1	-	Quest PharmaTech, Inc.	-
Gastrointestinal Neoplasms	Preclinical	CA	Quest PharmaTech, Inc.	-
Lung Cancer	Preclinical	CA	-	-
Prostatic Cancer	Discovery	CA	-	-

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