Chitosan-based mucoadhesive gel for oral mucosal toluidine blue O delivery: The influence of a non-ionic surfactant

Photodynamic therapy (PDT) has been successfully employed in the treatment of oral cancer. Toluidine blue O (TBO) is a photosensitizer (PS) that has exhibited remarkable photocytotoxicity in a variety of tumour cells; however, its physicochemical properties, as well as the physicochemical properties of oral mucosa, prevent the drug from reaching the target site at a therapeutic concentration.The aim of this study was to evaluate the influence of Tween 80^® (TW), which has shown potential as a penetration enhancer, on the mucosal retention of TBO for the PDT of oral cancer. 4% Chitosan-based mucoadhesive gels (CH gels) containing or not 5%TW were prepared (both containing 1%TBO), and their physicochemical properties (pH, rheology and mucoadhesion), TBO in vitro release profiles and TBO in vitro mucosal retention were evaluated. In vivo mucosal penetration studies of TBO followed by laser exposition were also carried out.The results showed that 4%CH gels containing 5%TW and 1%TBO have adequate mucoadhesive and rheological properties for oral mucosa use, although they present a slightly acid pH. TBO release studies showed that TW reduces TBO release, but it prolongs TBO release and increases TBO retention in the mucosa. In vivo studies showed that 4%CH gels containing 5%TW and 1%TBO cause an increase in the number of apoptotic cell, after laser exposition.In summary, 4%CH gels containing 5%TW may be a promising vehicle to optimize the penetration of TBO in oral mucosa and to improve the PDT response for the treatment of oral cancer.     

Photodynamic therapy in the management of pre-malignant head and neck mucosal dysplasia and microinvasive carcinoma

The management of head and neck mucosal dysplasia and microinvasive carcinoma is an appealing strategy to prevent the development of invasive carcinomas. While surgery remains the standard of care, photodynamic therapy (PDT) offers several advantages including the ability to provide superficial yet wide field mucosal ablative treatment. This is particularly attractive where defining the extent of the dysplasia can be difficult. PDT can also retreat the mucosa without any cumulative fibrotic complications affecting function. To date, clinical experience suggests that this treatment approach can be effective in obtaining a complete response for the treated lesion but long term follow-up is limited. Further research efforts are needed to define not only the risk of malignant transformation with PDT but also to develop site specific treatment recommendations that include the fluence, fluence rate and light delivery technique.     

Photodynamic therapy,a promising treatment approach for cutaneous infectious granulomas

Cutaneous infectious granulomas are mainly caused by fungi and bacteria. Antibiotics are the primary therapeutic choices for these diseases, but drug-resistant pathogens have become increasingly prevalent. Thus, there is a need to explore novel approaches to treat cutaneous infectious granulomas. Photodynamic therapy (PDT) is widely used as a treatment for various kinds of skin diseases, and evidence has been accumulating that PDT is also effective for the treatment of cutaneous infectious granulomas. In this narrative review, we sought to summarize the recent literature concerning the applications and mechanisms of PDT in the treatment of cutaneous infectious granulomas. Clinical and basic research has demonstrated that PDT is an effective approach in treating fungal infections such as sporotrichosis and chromoblastomycosis. In addition, PDT is also used to treat atypical mycobacterial infections such as Mycobacterium marinum. PDT can significantly shorten the duration of antibiotics treatment, resulting in diminishment of adverse effects. The potential mechanisms of PDT are to kill the pathogens directly or elicit modulatory effects on the immune microenvironments. We conclude that PDT is a promising therapeutic choice for the treatment of cutaneous infectious granulomas.     

Severe acute airway obstruction and respiratory failure with fibrous plug following photodynamic therapy (PDT): Indication for early bronchoscopy and debridement

IntroductionPDT is a safe procedure with most post procedural complications reported as minor. We report a case of severe acute stridor and trachea-bronchial airway obstruction with mucosal sloughing and fibrous plugs resulting in respiratory failure within three hours following PDT. To our knowledge this is the first reported case where stridor and acute respiratory failure resulted within hours following PDT treatment.Case ReportA 65 year old female with previous right pneumonectomy presented with followup bronchoscopy confirming reoccurrence of carcinoma proximal and distal to the anastomosis. A standard photofrin (Porfimer sodium) was administered at 2mg/kg body weight 48 hours prior to her PDT treatment. Three hours following the procedure, patient become acutely stridurous and was subsequently intubated. Bedside bronchoscopy was performed through the endotracheal tube. During the bronchoscopy thick tracheal plugs were retrieved and slough adjacent to the treatment site was noticed which was debrided. Patient underwent 7 bronchoscopies with debridement before she was discharged.ConclusionAirway obstruction (with NSCLA) is an indication as well as complication (with mucosal debris) of PDT. FDA has advised bronchoscopy at 48-72 hours post procedure, however early intervention with bronchoscopy and debridement should be considered to relieve tracheal bronchial airway obstruction and removal of accessory debris and mucosal slough.     

The current role of photodynamic therapy in oesophageal dysplasia and cancer

Over the last 15 years photodynamic therapy (PDT) has become a viable treatment for pre-malignant and malignant disease of the oesophagus. Its initial use was in the palliation of oesophageal malignant obstruction bringing improved swallowing hence increasing nutritional intake and improving general quality of life. As the therapeutic boundaries of PDT have stretched, current studies look at the role of PDT in the treatment of pre-malignant dysplastic Barrett's epithelium and early malignancy as a curative mucosal ablative technique. As a curative treatment in early oesophageal cancer, PDT provides an alternative treatment to oesophagectomy for those more elderly or less medically fit patients.This paper reviews the uses of photodynamic therapy in oesophageal cancer with reference to the available publications on its use in the palliation of oesophageal cancer and treatment of early cancer and high grade dysplasia in Barrett's mucosa.     

Photodynamic therapy in oral potentially malignant disorders—Critical literature review of existing protocols

IntroductionOral cancer is a serious public health issue. Apart from its high rate of prevalence, incidence and mortality, it can often result in more complex and expensive treatment when diagnosed late. Potentially malignant disorders (PMDs) can precede oral cancer, and are usually treated by surgical excision. However, in many cases patients are elderly and multiple interventions may be required. Photodynamic therapy (PDT) is a simple alternative, which has been successfully used in the treatment of oral PMDs.ObjectiveDue to the lack of standardization regarding photosensitizers (PTSs), types of irradiation, and methods of application, the objective of this study was to analyze existing PDT protocols in an attempt to identify the one that demonstrates greater efficiency, reliability and feasibility in the treatment of oral PMDs for both researchers and clinicians.MethodsOriginal clinical studies published only in English between 1993 and 2016 were searched in Pubmed/Medline database using the following keywords: photodynamic therapy; oral potentially malignant disorder; oral premalignant lesions. Review articles; experimental studies; case-reports; commentaries; and letters to the Editor were excluded from the selection.Results and conclusionBased on the 16 studies selected, the topical 5-ALA-20% PTS, associated to a LED light applied for 15 min with a 7-day interval between sessions emerged as the most frequently used PDT protocol, with satisfactory results. Due to its low rate of side effects, this PDT protocol presents good potential for the treatment of oral PMDs. Further clinical studies are required to ascertain its long-term validity in preventing oral cancer.     

Photodynamic therapy (PDT) as a cancer treatment for global health: Insights from development of low-cost technology for image-guided PDT of early oral cancer in India

The World Health Organization reports that more than 60% of new cancer cases and 70% of deaths annually occur in low and middle income countries (LMICs). A lack of medical infrastructure for timely diagnosis and treatment of cancer in LMICs drives this disparity and motivates the development of low-cost technologies that are specifically adapted for use in resource-limited settings. We have developed technology to enable use of photodynamic therapy (PDT) with aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) for treatment of early-stage oral malignancy in India, which has been described as the “oral cancer capital of the world.” As a light-based approach PDT is inherently conducive to LMIC adaptation using LEDs as a low-cost source for visible wavelengths that can readily provide irradiance in the range of 10’s of mW/cm² for small lesions. Our team developed a portable, battery-powered, fiber-coupled 635nm LED light source with a system of interchangeable 3D printed applicators for ergonomic light delivery to lesions of varying size and position in the oral cavity. The system uses an embedded microcontroller and Bluetooth to interface with a smartphone while an attachment for imaging PpIX fluorescence is used for treatment guidance and monitoring. Clinical evaluation in partnership with collaborators in India has shown excellent outcomes, with complete tumor response in 73% of oral cancer patients following a single PDT treatment. Here we discuss ongoing technology development to continue to optimize intraoral PDT light delivery and improve image guidance during treatment, as well as challenges and opportunities moving forward for broader implementation and adaptation to other indications.     

Photodynamic therapy and Acyclovir in the treatment of recurrent herpes labialis: A controlled randomized clinical trial

BackgroundHerpes Simplex Virus Type 1 (HSV-1) is one of the most widespread infections that can effect the orofacial region. Recurrent infection is considered a life-long oral health problem, leading to pain, discomfort, and social restriction due to esthetic features when active. Effective therapies are needed. This study aimed to compare photodynamic therapy (PDT), Topical Acyclovir (AC), and the association of both in the healing process and self-reported symptomologies of HSV-1 recurrences.MethodsPatients were randomly assigned into 3 groups (n = 25): PDT (low-power laser, 660 nm, 40 mW, 120 J/cm², 4.8 J, 120 s per point) and methylene blue (0.005 %) as photosensitizer; AC (5%); PDT + AC.Data concerning lesion size, healing time, and self-reported healing parameters, such as pain, tingling, and edema were taken every day up to complete healing for all studied groups.ResultsThere was no significant difference in healing time and pain between groups. AC group showed a significant minor reduction of the lesion compared to the AC-PDT group on day 1. Regarding edema and tingling, the comparison of treatments showed a statistical difference only on day 1, where PDT showed better results.ConclusionWith all the limitations of this study, it can be concluded that only on day 1 PDT showed positive effects in the treatment of herpes lesions in comparison to AC.     

口腔黏膜肿瘤的光动力治疗

目的观察光动力疗法治疗口腔黏膜癌前病变及口腔癌的临床疗效。方法临床及病理确诊的口腔黏膜扁平苔藓和鳞癌患者各1例,静脉注射光敏剂PSD-007 5 mg/kg后6 h,应用波长630 nm的半导体激光以点状光纤照射,激光功率密度150 mW/cm2,每个光斑照射10～30 min,能量密度90～270 J/cm2。观察患者术中和术后的不良反应。术后4～5周进行近期临床疗效评价。结果 2例患者累计治疗18处病灶,其中15处病灶经1次治疗,2处病灶经2次治疗,1处病灶经3次治疗后痊愈,未见瘢痕形成。2例患者病灶愈合后均无口腔功能及感觉变化。结论光动力疗法具有靶向性好、选择性高、安全可靠、创伤小、可重复应用和对口腔功能无明显损害等优点,是一种安全、值得推广的治疗口腔黏膜癌前病变和口腔癌的高效疗法。     

Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia

Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic.     

The use of photodynamic therapy using 630 nm laser light and porfimer sodium for the treatment of oral squamous cell carcinoma

PDT has been demonstrated in clinical studies to be an efficacious method for the treatment of dysplastic, microinvasive and early forms of cancer. The advantage of PDT for early carcinomas of the oral cavity is the ability to preserve normal tissues while effectively treating cancers up to 1cm in depth. The case presented here successfully demonstrates the ability to use PDT to treat maxillary gingival squamous cell carcinoma thereby sparing the use of surgery or radiation therapy at this point in the management of the disease.     

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up

ObjectivesPhotodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up.Materials and methodsThirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm² using a 630-nm wavelength excimer dye laser.ResultsSix months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed.ConclusionPDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.     

Photodynamic therapy for onychomycosis: A systematic review

Other than a cosmetic concern, Onychomycosis is also a prevalent nail disease, which is extremely difficult to treat, and sometimes is refractory to conventional therapy. Moreover, many patients are not eligible to take oral antifungals owing to polypharmacy and comorbidities. Systemic side effects seen with oral antifungals have lead to patient nonadherence and adverse events. Therefore, newer therapies are being investigated for onychomycosis that would be free of systemic complications posed by oral therapy. Photodynamic therapy (PDT) is one of those being currently studied, which involves the use of photosensitizer and a light source to excite the photosensitizer to generate reactive oxygen species. The present review will put some light on PDT as an upcoming treatment modality for onychomycosis. We performed a systematic review of the literature to find the articles relevant to the use of PDT for onychomycosis. From the primary search of 43 articles, 17 papers are included in this review.     

Does HPV infection have impact on results of photodynamic treatment of vulvar lichen sclerosus?

BackgroundThe association between lichen sclerosus (LS) and human papilloma virus (HPV) infections remains unclear. The co-occurrence of both pathologies may impact treatment and prognosis.This study aimed to assess the results of photodynamic therapy (PDT) for vulvar LS and the effect of incidence of HPV infection on the results of treatment and duration of remission.MethodsA total of 73 patients with LS were included in the study. In each patient, 14 types of HPV were detected. PDT was performed using the PhotoDyn 501, which emits light at 630 nm wavelength and power density of 204 mW/cm². Focal lesions were exposed for 10 min once weekly for a total of 10 weeks. The complete treatment cycle was repeated after 3 months, whenever required. The biopsy was repeated after completion of treatment.ResultsThe number of treatment cycles for HPV-positive and HPV-negative patients were not statistically different (cases after one or two PDT cycles). An exception was a group of patients with LS requiring three PDT cycles. Analysis of remission period considering HPV results (positive vs. negative) did not reveal a significant statistical difference. Mean remission period among HPV-negative patients was longer in comparison to remission time for those with positive HPV results (14 ± 9 vs. 11 ± 9 months).ConclusionsPDT may be a promising, effective, and safe method for the treatment of LS regardless of HPV infection.     

Efficacy of photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical high-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study

BackgroundThe current principle of clinical management of cervical high-grade squamous intraepithelial lesion(HSIL) is surgical excision. However excisional procedures of the uterine cervix may have a negative impact on fertility. Topical photodynamic therapy(PDT) is a non-invasive and selective tissue destruction. We investigated the clinical efficacy of PDT for cervical HSIL with high-risk human papilloma virus(HPV) infection.MethodsA retrospective study consisting of 96 patients aged 20–50 years with a histologically confirmed cervical HSIL with high-risk HPV infection from July 2018 to June 2022 was carried out. Patients were treated with six times of 20% 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) at intervals of 7–14 days. Three months after treatment, the effect was evaluated through HPV typing and colposcopy directed biopsy. Six and twelve months after treatment, TCT and HPV tests were carried out.ResultsThree months after 5-ALA PDT treatment, among 96 HSIL with high-risk HPV infection patients, the total lesion regression rate was 89.58%(86/96), and the HPV clearance rate was 79.17 % (76/96) at 3 months follow-up. At 6 and 12 months follow-up, the patients who was HSIL pathological regression and negative HPV at 3 months follow-up continued negative results in both TCT and HPV. All patients with ineffective 5-ALA PDT treatment had persistent HPV infections. There was no significant difference in the HSIL regression rate and HPV clearance rate among different age groups. The main side effects of PDT were abdominal pain and increased vaginal secretions. Univariate analysis showed that the different severity of cervical cytology was associated with lesion regression rate in 5-ALA PDT treatment. The HSIL regression rate of TCT<ASC-H was higher than that of TCT≧ASC-H(94.59% vs 72.72%; P<0.01).Multicentric lesions,the proportion of visible lesion size in ectocervical size≥24.59%, size of visible lesion ≥1.23cm² and maximum linear length of visible lesion ≥0.90cm were risk factors of HSIL persistence after 5-ALA PDT treatment (P<0.05).Conclusion5-ALA PDT can be a safe and efficient treatment for cervical HSIL who wish to preserve fertility. 5-ALA PDT did not appear to create cervical damage and have negligible side effects. But we need evaluate the type of transformation zone, the visible lesion size, the location of lesion,baseline status of TCT and histological results before 5-ALA PDT treatment.     

Evaluation of photodynamic therapy in treatment of oral erosive lichen planus in comparison with topically applied corticosteroids

BackgroundThe treatment of erosive oral lichen planus represents a therapeutic challenge. Despite numerous existing remedies, some of these treatments display disappointing results. Since it is a chronic disease with no current cure, the best treatment should target mainly the reduction of the duration and severity of symptomatic outbreaks with minimal side effects. To date, corticosteroids remain the first choice of treatment for oral lichen planus (OLP) patients. Although, topical corticosteroids have been found to be the safest and the most successful agents in the treatment of OLP, their prolonged use may cause mucosal problems and may lead to systemic complications. Recently, the use of photodynamic therapy has been well introduced in the treatment of oral diseases. Our clinical study was done to evaluate clinically the effect of photodynamic therapy mediated by methylene blue (MB-PDT) on signs and symptoms of erosive oral lichen planus (EOLP) lesions in comparison with the conventional topical corticosteroids (TC) treatment. The present work tried this recent modality of treatment to overcome the disadvantages of TC.Material and methodsTwenty patients with clinical and histological diagnosis of EOLP were selected from Oral Medicine and periodontology department in Faculty of Dentistry, Alexandria University in a randomized parallel study design. They were divided into two groups; group A (control group) involved ten patients who were instructed to use the conventional TC (kenakort A-orabase). While, group B (study group) contained ten patients who received PDT using diode laser 660 nm mediated by methylene blue (MB).ResultsBoth groups presented statistically significant difference from baseline to follow up periods. But, the MB-PDT in treatment of EOLP showed more remarkable reduction in pain and lesion scores in comparison with corticosteroids treatment.ConclusionThe results of this study allow the conclusion that the MB-PDT is considered to be a better treatment for OELP in comparison with TC because it is much more effective in pain reduction and lesion regression.     

Clinical evaluation of a mobile,low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India

Background: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery.Methods: 30 patients with T₁N₀M₀ buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps. Tumour limits were defined by external ultrasound (US), white light photos and increased tumour fluorescence after oral administration of the photosensitising agent ALA (60 mg/kg, divided doses), monitored by a smartphone fluorescence imaging device. 100 J/cm² LED light (635 nm peak) was delivered followed by repeat fluorescence to assess photobleaching. US and biopsy were repeated after 7–17 days. This trial is registered with ClinicalTrials.gov, NCT03638622, and the study has been completed.Findings: There were no significant complications or discomfort. No sedation was required. No residual disease was detected in 22 out of 30 patients who completed the study (26 of 34 lesions, 76% complete tumour response, 50 weeks median follow-up) with up to 7.2 mm depth of necrosis. Treatment failures were attributed to large tumour size and/or inadequate light delivery (documented by limited photobleaching). Moderately differentiated lesions were more responsive than well-differentiated cancers.Interpretation: This simple and low-cost adaptation of fluorescenceguided PDT is effective for treatment of early-stage malignant oral lesions and may have implications in global health.     

Revisiting the evidence of photodynamic therapy for oral potentially malignant disorders and oral squamous cell carcinoma: An overview of systematic reviews

BackgroundThis study summarized the available evidence about the use of photodynamic therapy (PDT) for the management of oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC).MethodsAn overview of systematic reviews was undertaken based on the 2020 PRISMA statement. Electronic searches were performed in five databases. Studies published up to November 2022 were included. Risk of bias was assessed with the AMSTAR 2 tool.ResultsA total of 30 studies enrolling 9,245 individuals with OPMD (n = 7,487) or OSCC (n = 1,758) met the selection criteria. All studies examined the efficacy and/or safety of PDT. OPMD were investigated individually in 82.8% of the studies, the most common being oral lichen planus and actinic cheilitis. OSCC was addressed separately in 10.3% of the studies, while only 6.9% evaluated both OPMD and OSCC. Fourteen different types of photosensitizers were described. PDT was used according to the following setting parameters: 417–670 nm, 10–500 mW/cm², 1.5–200 J/cm², and 0.5–143 min. Regarding OPMD, leukoerythroplakia showed the best response rates, while oral lichen planus presented a partial or no response in nearly 75% of documented cases. A complete response was observed in 85.9% of OSCC cases, while 14.1% had no resolution.ConclusionOverall, the response to PDT depended on the type of OPMD/OSCC and the parameters used. Although PDT is an emerging candidate for the treatment of OPMD and OSCC, there is heterogeneity of the methodologies used and the clinical data obtained, particularly regarding the follow-up period.     

Study of hematoporphyrin monomethyl ether-mediated blue-light photodynamic therapy in the treatment of oral ulcers infected with Staphylococcus aureus: In vivo evaluation.

Clinical suppurative infection is mainly caused by Staphylococcus aureus. Although many antibiotics can be used to kill S. aureus, the resulting resistance problem is difficult to solve. Therefore, it is necessary to seek a new sterilizing method to solve the problem of drug resistance of S. aureus and improve the therapeutic effect of infectious diseases. Photodynamic therapy (PDT) has become an alternative for the treatment of a variety of drug-resistant infectious diseases due to its advantages of non-invasive, specific targeting, and no drug resistance. We have confirmed the advantages and experimental parameters of blue-light PDT sterilization in vitro experiments. This study aimed to treat buccal mucosa ulcer of hamster infected with S. aureus according to the parameters obtained in vitro experiment, and observe the bactericidal effect of hematoporphyrin monomethyl ether (HMME) mediated blue-light PDT in vivo and its therapeutic effect on tissue infection. The results indicated that HMME mediated blue-light PDT can effectively kill S. aureus in vivo and promote the healing of the oral infectious wound.The study findings lay a foundation for carrying out more HMME mediated blue-light PDT sterilizing therapy.