Cubic phase gel as a drug delivery system for topical application of 5-ALA, its ester derivatives and m-THPC in photodynamic therapy (PDT)

Turchiello, Rozane de Fátima; Vena, Flávia Cristina Bonilha; Maillard, Ph.; Souza, Carla; Bentley, Maria Vitória Lopes Badra; Tedesco, Antônio Cláudio

doi:10.1016/s1011-1344(03)00022-8

Cited by 68 publications

(33 citation statements)

References 20 publications

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“…MO structured in a cubic phase gel (70:30, MO:water) provided an increase of in vitro and in vivo skin uptake for 5-ALA and its ester derivatives (hexyl, octyl and decyl esters), m-tetrahydroxyphenylchlorin and an in vivo increase of protoporphyrin IX accumulation [33]. Similarly, compared to standard ointments, a similar effect of in vivo protoporphyrin IX accumulation was observed when an MO cubic phase was used as a delivery vehicle for 5-ALA and methyl-5-ALA [13].…”

Section: Discussionmentioning

confidence: 99%

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Praça¹,

Medina²,

Petrilli³

et al. 2012

CNANO

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Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were performed using a Franz's cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and hexagonal phases showed particles of nanometer size, approximately 224 ±10 nm and 188 ± 10 nm, respectively. In vitro skin retention experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal). The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.Keywords: Liquid crystalline phases, nanodispersion, skin cancer, skin penetration, photodynamic therapy, zinc phthalocyanine. INTRODUCTIONTopical photodynamic therapy (PDT) has been applied to almost every type of superficial nonmelanoma skin cancer and numerous benign skin disorders [1][2]. PDT is based on the administration of a photosensitizing drug and its selective retention in malignant tissue and its subsequent activation by light at specific wavelengths, causing cell death by the production of free radicals and/or reactive oxygen species [3,4]. Numerous strategies have been studied in recent years in attempts to improve the accumulation of photosensitizers and their precursors in the skin, including the use of microemulsions [5] [13][14][15]. Lipophilic phthalocyanines (e.g., zinc and chloroaluminum compounds) have been widely used as photosensitizers in preclinical studies of PDT for the treatment of skin cancer [16,17]. In contrast, the water-soluble zinc phthalocyanine tetrasulfonate (ZnPcSO 4 ) has displayed high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain and ocular tumors [18]. However, with exception of a few studies [19][20][21], there is a lack of data on the application of ZnPcSO 4 in PDT for skin cancer.Their ability to control the release of dru...

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Section: Discussionmentioning

confidence: 99%

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Praça¹,

Medina²,

Petrilli³

et al. 2012

CNANO

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“…Typically, ALA is formulated as a liquid or semi-solid preparation and applied to the skin for 3-6 hours. Quantitative methods employing HPLC with fluorescence detection have been successfully used to determine the stability of ALA in such topical preparations [21]. In addition, ALA quantification allows the determination of partitioning coefficients, drug solubility, drug release from a given formulation and drug permeation across skin membranes [16].…”

Section: Discussionmentioning

confidence: 99%

“…(3a, 4) it is apparent that the derivatisation procedure allows for much greater sensitivity for the detection of ALA compared to the two esters studied. Turchiello et al [21] demonstrated that the fluorescence intensities of 4 mM solutions of ALA esters were approximately one order of magnitude less than that of a 4 mM solution of ALA. Merclin et al [37] reported linear calibration ranges for ALA and m-ALA detection, following derivatisation with AA reagent. The authors reported that the lower limit of the m-ALA calibration profile was approximately 35 times greater than that seen for ALA.…”

Section: Discussionmentioning

confidence: 99%

“…The procedure used by Mauzerall and Granick for ALA quantification has been adapted to allow determination of ALA esters in solution by UV spectroscopy [20]. In contrast, Turchiello et al [21] derivatised ALA esters with acetyl acetone and formaldehyde and quantified the derivative using spectrofluorimetry (excitation 378 nm, emission 466 nm). However, to differentiate between ALA and its esters, an appropriate separation technique is required.…”

Section: Introductionmentioning

confidence: 99%

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Practical Considerations in the Pharmaceutical Analysis of Methyl and Hexyl Ester Derivatives of 5-Aminolevulinic Acid

Morrow¹,

McCarron²,

Woolfson³

et al. 2009

TOACJ

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Photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA), a water-soluble precursor of the potent endogenous photosensitiser, protoporphyrin IX (PpIX), is a treatment and diagnostic tool for premalignant and malignant skin cancers. However, to improve drug delivery to deeper skin lesions, more lipophilic ALA esters have been investigated. Owing to the necessity in drug delivery research for efficient and validated assays for ALA esters in solution, this paper aims to describe optimised protocols to quantify the methyl and hexyl esters of ALA.ALA esters were derivatised using acetyl acetone and formaldehyde reagents and analysed using reversed phase HPLC. For the first time, the significance of ALA-impurities in ester samples has been highlighted. Furthermore, it was shown that for a given concentration, peak areas obtained for ALA-esters were significantly smaller than those obtained for ALA (p < 0.05). This may be due to parent drug undergoing the derivatisation reaction more efficiently or because the ALAderivate is inherently more fluorescent than the ester derivatives. The method was optimised to give acceptable intra-and inter-day variability (CV values < 5%) and the limits of detection and quantification were determined for both drugs.The validated methods were used to determine the release profiles of ALA, m-ALA and h-ALA from an o/w cream formulation. The percentage of drug loading released after five hours across a model membrane was in the order of ALA (45.2%) > m-ALA (38.3%) > h-ALA (33.9%). These findings may explain why, historically, some of the benefits seen with ALA-esters using cell culture models have not been demonstrated in vivo.

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“…The choice of the source of light must be based on the absorption by the photosensitizer drug, the purpose of the action (treatment of a small cancerous lesion or wound healing stimulation), characteristics of the lesion or wound (local, size, accessibility, and characteristics of the tissue) costs and size [7]. A wide number of photosensitizers in different drug delivery systems (DDSs) have been tested for PDT [25][26][27][28][29]. Among them, phthalocyanines (Pc) have been under investigation as promising second-generation photosensitizers, not only for PDT, but also for other applications.…”

Section: Interaction Of Light In the Skinmentioning

confidence: 99%

Low Level Energy Photodynamic Therapy for Skin Processes and Regeneration

Tedesco¹,

Jesus²

2017

Photomedicine - Advances in Clinical Practice

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Skin is the largest human organ and displays multiple functions involving structure and protection against external agents that may affect the body. Solar radiation accelerates the normal aging process and may even cause great damage leading to many different cutaneous diseases and skin cancer. Moreover, a wound in the skin may be an open channel for the access of pathogens usually exposing blood vessels for infections and causing serious complications. For many reasons, regulatory skin processes are of great deal in different approaches: basic antiaging, wound healing, and skin cancer. In a good way, photoprocesses with specific wavelength at low energy levels associated with photoactive compounds are known to cause the opposite effect, promoting the healing of cutaneous diseases and leading to well-defined outcomes in rejuvenation and antiaging. This chapter will discuss the most relevant topics in photo skin regeneration using low energy levels associated with photodynamic therapy (PDT), which emerged as a combination to potentialize molecules with the already known effects of PDT and low level laser therapy (LLLT) in the treatment of skin pathologies, known as a photobiomodulation process.

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Cubic phase gel as a drug delivery system for topical application of 5-ALA, its ester derivatives and m-THPC in photodynamic therapy (PDT)

Cited by 68 publications

References 20 publications

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Practical Considerations in the Pharmaceutical Analysis of Methyl and Hexyl Ester Derivatives of 5-Aminolevulinic Acid

Low Level Energy Photodynamic Therapy for Skin Processes and Regeneration

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