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Therapeutic Delivery Jun 2024Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical and systemic treatments are preferred to address these sight-threatening... (Review)
Review
Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical and systemic treatments are preferred to address these sight-threatening conditions. However, the unique anatomy of the eye presents challenges for drug delivery. Various ophthalmic ointment formulations have been developed to enhance bioavailability in the eye to prolong residence time and improve corneal permeability. This article explores a wide range of ocular diseases affecting individuals globally and how ointments are used to manage them. From eye to ocular barriers, this review focuses on published scientific research and formulation strategies for severe ocular complications using conventional topical ointments. Additionally, it delves through patented technologies and marketed formulations supporting the use of ointments in ocular drug delivery.
PubMed: 38888757
DOI: 10.1080/20415990.2024.2346047 -
Drugs in R&D Jun 2024PD-1 inhibitors have revolutionized cancer therapies and are being used to treat an expanding array of cancers. To best serve patients, clinicians should be familiar...
BACKGROUND AND OBJECTIVE
PD-1 inhibitors have revolutionized cancer therapies and are being used to treat an expanding array of cancers. To best serve patients, clinicians should be familiar with the spectrum of skin manifestations associated with PD-1 inhibitor therapy. Here, we report a unique case of hypertrophic lichen planus (HLP) in a 64-year-old man treated with pembrolizumab; the presentation initially suggested a squamous cell carcinoma (SCC) morphology, then evolved into a morphology more typical of hypertrophic lichen planus. This case underscores the need for caution in diagnosing eruptive SCCs associated with PD-1 inhibitor therapy. In such instances, maintaining a high suspicion for lichenoid reactions as sequelae of PD-1 inhibitor treatment and starting an empiric trial of therapy for lichenoid dermatitis may be warranted to ensure timely management of lesions.
METHODS
We describe a case of hypertrophic lichen planus mimicking squamous cell carcinoma in the setting of PD-1 inhibitory therapy with pembrolizumab. A PubMed literature review was conducted to identify other cases and determine the incidence of lichenoid reactions imitating squamous cell carcinoma in the setting of PD-1 inhibitor use.
RESULTS
Our case is one of the few available pieces of literature describing eruptive hypertrophic lichen planus imitating SCC in the setting of PD-1 inhibitor use. Initial skin nodule biopsy appeared histologically compatible with squamous cell carcinoma. Repeat biopsy of the skin lesions revealed histological features consistent with hypertrophic lichen planus. Over time, lower extremity lesions evolved into a more typical appearance of hypertrophic lichen planus. Treatment with topical 0.05% clobetasol ointment and oral acitretin 25 mg led to complete resolution of lesions within 2-3 months.
CONCLUSIONS
This case underscores the significance of maintaining vigilance for lichenoid reactions as potential sequelae of PD-1 inhibitor therapy. It highlights the variability in initial presentation and the potential for lesions to transform over time. Timely recognition and appropriate management, including high-potency topical corticosteroids and oral acitretin, are crucial for achieving favorable outcomes in patients experiencing such reactions. More studies are necessary to fully analyze the rate of HLP occurrence as a consequence of PD-1 inhibitor use.
PubMed: 38877280
DOI: 10.1007/s40268-024-00461-x -
International Journal of Biological... Jun 2024Atopic dermatitis (AD) is a chronic cutaneous disease with a complex underlying mechanism, and it cannot be completely cured. Thus, most treatment strategies for AD aim...
Atopic dermatitis (AD) is a chronic cutaneous disease with a complex underlying mechanism, and it cannot be completely cured. Thus, most treatment strategies for AD aim at relieving the symptoms. Although corticosteroids are topically applied to alleviate AD, adverse side effects frequently lead to the withdrawal of AD therapy. Tacrolimus (TAC), a calcineurin inhibitor, has been used to treat AD, but its high molecular weight and insolubility in water hinder its skin permeability. Herein, we developed and optimized TAC-loaded chitosan-based nanoparticles (TAC@CNPs) to improve the skin permeability of TAC by breaking the tight junctions in the skin. The prepared nanoparticles were highly loadable and efficient and exhibited appropriate characteristics for percutaneous drug delivery. TAC@CNP was stable for 4 weeks under physiological conditions. CNP released TAC in a controlled manner, with enhanced skin penetration observed. In vitro experiments showed that CNP was non-toxic to keratinocyte (HaCaT) cells, and TAC@CNP dispersed in an aqueous solution was as anti-proliferative as TAC solubilized in a good organic solvent. Importantly, an in vivo AD mouse model revealed that topical TAC@CNP containing ~1/10 of the dose of TAC found in commercially used Protopic® Ointment exhibited similar anti-inflammatory activity to that of the commercial product. TAC@CNP represents a potential therapeutic strategy for the management of AD.
PubMed: 38866268
DOI: 10.1016/j.ijbiomac.2024.133005 -
The AAPS Journal Jun 2024Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating...
Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating phenylpropanoids-Eugenol and Cinnamaldehyde-with positively-charged silver nanoparticles was synthesized. The process began with the synthesis and characterization of nano-silver, aimed at ensuring the effectiveness and safety of the nanoparticles in biological applications. Subsequent experiments determined the minimum inhibitory concentration (MIC) against pathogens such as Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. These MIC values of all three active leads guided the strategic formulation of an ointment base, which effectively integrated the bioactive components. Evaluations of this nano-ointment revealed enhanced antimicrobial activity against both clinical and reference bacterial strains and it maintained stability after freeze-thaw cycles. Furthermore, the ointment demonstrated superior in-vitro diabetic wound healing capabilities and significantly promoted angiogenesis, as shown by enhanced blood vessel formation in the Chorioallantoic Membrane assay. These findings underscore the formulation's therapeutic potential, marking a significant advance in the use of nanotechnology for topical wound care.
Topics: Silver; Wound Healing; Microbial Sensitivity Tests; Metal Nanoparticles; Animals; Ointments; Acrolein; Candida albicans; Anti-Infective Agents; Pseudomonas aeruginosa; Administration, Topical; Humans; Anti-Bacterial Agents; Staphylococcus aureus
PubMed: 38862870
DOI: 10.1208/s12248-024-00936-4 -
Actas Dermo-sifiliograficas Jun 2024Dermatologic surgery is associated with a very low risk of complications. There is no widely accepted, evidence-based protocol with recommendations for postoperative...
Dermatologic surgery is associated with a very low risk of complications. There is no widely accepted, evidence-based protocol with recommendations for postoperative wound care after dermatologic surgery. In this narrative review, we will be discussing the evidence on surgical wound care products and procedures. Overall, we found relatively few studies and, in many cases, a lack of statistically significant differences, possibly because of the low rate of complications. We'll be discussing the evidence on when we should initiate wound care procedures and their frequency, the type of ointment and antiseptics that should be applied, and the type of dressings that should be used. Despite the very few studies available on postoperative wound care following dermatologic surgery, there is sufficient evidence as to not recommend the use of prophylactic topical antibiotics. We also analyze the currently available evidence on surgical wound care in special situations, such as management of skin grafts, partial skin graft donor sites, xenografts/biomembranes, and surgical wounds to the legs.
PubMed: 38857845
DOI: 10.1016/j.ad.2024.05.020 -
Cureus May 2024Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the...
Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.
PubMed: 38854231
DOI: 10.7759/cureus.59878