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1.
Int J Biol Macromol ; 279(Pt 1): 134973, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39182897

ABSTRACT

Untreated or poorly managed chronic wounds can progress to skin cancer. Topically applied 5-fluorouracil (5-FU), a nonspecific cytostatic agent, can cause various side effects. Its high polarity also results in low cell membrane affinity and bioavailability. Hydrogel, used for its occlusive effect, is one platform for treating chronic wounds combined with PEGylated liposomes (LPs), developed to increase drug-skin affinity. This research aimed to develop a novel hydrogel forming chitosan-based microneedles (HFM) chemowrap patch containing 5-FU PEGylated LPs, improving 5-FU efficiency for pre-carcinogenic and carcinogenic skin lesions. The results indicated that the 5-FU-PEGylated LPs-loaded HFM chemowrap patch exhibited desirable physical and mechanical characteristics with complete penetration ability. Furthermore, in vivo skin permeation studies demonstrated the highest percentage of 5-FU permeated the skin (42.06 ± 11.82 %) and skin deposition (75.90 ± 1.13 %) compared to the other treatments, with demonstrated superior percentages of complete wound healing in in vivo (47.00 ± 5.77 % wound healing at day 7) and in NHF cells (92.79 ± 7.15 % at 48 h). Furthermore, 5-FU-PEGylated LPs-loaded HFM chemowrap patches exhibit efficient anticancer activity while maintaining safety for normal cells. The results also show that the developed formulation of a 5-FU-PEGylated LPs-loaded HFM chemowrap patch could enhance apoptosis higher than that of the 5-FU solution. Consequently, 5-FU PEGylated LPs-loaded HFM chemowrap patch represented a promising drug delivery approach for treating pre-carcinogenic and carcinogenic skin lesions.


Subject(s)
Chitosan , Fluorouracil , Hydrogels , Liposomes , Wound Healing , Fluorouracil/pharmacology , Fluorouracil/administration & dosage , Liposomes/chemistry , Chitosan/chemistry , Animals , Hydrogels/chemistry , Wound Healing/drug effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Mice , Humans , Skin/drug effects , Needles , Administration, Cutaneous , Male , Drug Delivery Systems , Polyethylene Glycols/chemistry
2.
Cureus ; 13(5): e15148, 2021 May 21.
Article in English | MEDLINE | ID: mdl-34178485

ABSTRACT

An estimated 20% of all malignant cutaneous neoplasms are diagnosed as squamous cell carcinoma (SCC). Chemotherapeutic wraps, or chemowraps, consist of application of topical 5-fluorouracil (5-FU) 5% cream along with occlusive zinc oxide and a compressive bandage (e.g., Unna boot). This treatment modality is often used as a less invasive option compared to surgery, especially in the presence of numerous SCCs. Cryotherapy, the use of liquid nitrogen gas, can be utilized to obliterate pre-malignant and malignant skin lesions. In this report, we present four cases in which females between the ages of 65 and 80 with multiple lower extremity SCCs were treated with cryotherapy prior to each chemowrap application, resulting in favorable clinical tumor improvement. Our observations indicate that cryotherapy may enhance the effectiveness of chemowrap treatment when used before each application. To our knowledge, the use of cryotherapy to synergistically enhance the efficacy of chemowraps has not yet been reported. We hypothesize that cryotherapy induces edema and first strips the outer, hyperkeratotic layers of skin, which facilitates deeper penetration of the 5-FU cream from chemowraps. Chemowraps may also relieve the pain associated with cryotherapy. Therefore, dual cryotherapy and chemowrap treatment may be considered to maximize skin penetration, thus minimizing the extent of surgical intervention in patients with a significant number of SCC lesions.

4.
Eur J Dermatol ; 27(6): 635-640, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29311041

ABSTRACT

Few satisfactory treatment options are available for widespread areas affected by multiple actinic keratoses (AKs). Our primary objective was to assess the response rate to weekly 5-fluorouracil (5-FU) chemowraps on widespread AK lesions, and secondarily to assess tolerability, the percentage of patients with recurrence and time to recurrence, the response rate for patients with associated Bowen's disease (BD), and the percentage of squamous cell carcinomas (SCCs) identified after treatment. We conducted an open study which included all the patients who had been treated with weekly 5-FU chemowraps in our department over the course of five years for areas of widespread AKs. The response rate for AKs was 60%, with 20% complete responses among 25 patients after an average of 9.6 sessions (1 to 64). The treatment had to be discontinued because of toxicity in four patients; one case of contact dermatitis, one case of erosive pustular dermatosis, and two cases of Grade 2 irritations. Invasive SCCs were identified in five patients after treatment cessation. The median recurrence-free survival was five months. A 64% response rate was achieved for associated BD. The weekly application of 5-FU under occlusion seems to be an interesting, well-tolerated therapeutic option for the treatment of widespread AKs.


Subject(s)
Dermatologic Agents/administration & dosage , Fluorouracil/administration & dosage , Keratosis, Actinic/drug therapy , Administration, Cutaneous , Aged , Aged, 80 and over , Drug Administration Schedule , Female , Humans , Keratosis, Actinic/pathology , Male , Middle Aged , Off-Label Use , Retrospective Studies , Treatment Outcome
5.
Australas J Dermatol ; 54(4): 313-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23651243

ABSTRACT

Elderly patients with extensive hypertrophic solar keratoses and squamous cell carcinoma on the lower legs can pose significant management challenges. Typically these patients require surgical treatment which is complicated by comorbidities and poor background lower leg skin. 5% fluorouracil chemowraps provides a useful alternative technique for the management of diffuse hypertrophic solar keratoses and as an adjuvant, and in some situations as a palliative treatment, for squamous cell carcinomas on the lower legs.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Keratosis, Actinic/drug therapy , Scalp , Skin Neoplasms/drug therapy , Administration, Cutaneous , Bandages , Humans , Leg
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