Dual-Drug-Loaded Topical Delivery of Photodynamically Active Lipid-Based Formulation for Combination Therapy of Cutaneous Melanoma.

Topical administration of anti-cancer drugs along with photodynamically active molecules is a non-invasive approach, which stands to be a promising modality for treating aggressive cutaneous melanomas with the added advantage of high patient compliance. However, the efficiency of delivering drugs topically is limited by several factors, such as penetration of the drug across skin layers at the tumor site and limited light penetrability. In this study, curcumin, an active anti-cancer agent, and chlorin e6, a photoactivable molecule, were encapsulated into lipidic nanoparticles that produced reactive oxygen species (ROS) when activated at 665 nm by near-infrared (NIR) light. The optimized lipidic nanoparticle containing curcumin and chlorin e6 exhibited a particle size of less than 100 nm. The entrapment efficiency for both molecules was found to be 81%. The therapeutic efficacy of the developed formulation was tested on B16F10 and A431 cell lines via cytotoxicity evaluation, combination index, cellular uptake, nuclear staining, DNA fragmentation, ROS generation, apoptosis, and cell cycle assays under NIR irradiation (665 nm). Co-delivering curcumin and chlorin e6 exhibited higher cellular uptake, better cancer growth inhibition, and pronounced apoptotic events compared to the formulation having the free drug alone. The study results depicted that topical application of this ROS-generating dual-drug-loaded lipidic nanoparticles incorporated in SEPINEO gel achieved better permeation (80 ± 2.45%) across the skin, and exhibited the improved skin retention and a synergistic effect as well. The present work introduces photo-triggered ROS-generating dual-drug-based lipidic nanoparticles, which are simple and efficient to develop and exhibit synergistic therapeutic effects against cutaneous melanoma.

Exploring the potential of polysaccharide-based hybrid hydrogel systems for their biomedical and therapeutic applications: A review.

Hydrogels are a versatile category of biomaterials that have been widely applied in the fields of biomedicine for the last several decades. The three-dimensional polymeric crosslinked hydrophilic structures of the hydrogel can proficiently hold drugs, nanoparticles, and cells, making them a potential delivery system. However, disadvantages like low mechanical strength, poor biocompatibility, and unusual in-vivo biodegradation are associated with conventional hydrogels. To overcome these hurdles, hybrid hydrogels are designed using two or more structurally different polymeric units. Polysaccharides, characterized by their innate biocompatibility, biodegradability, and abundance, establish an ideal foundation for the development of these hybrid hydrogels. This review aims to discuss the studies that have utilized naturally occurring polysaccharides to prepare hybrid systems, which were aimed for various biomedical applications such as tissue engineering, bone and cartilage regeneration, wound healing, skin cancer treatment, antimicrobial therapy, osteoarthritis treatment, and drug delivery. Furthermore, this review extensively examines the properties of the employed polysaccharides within hydrogel matrices, emphasizing the advantageous characteristics that make them a preferred choice. Furthermore, the challenges associated with the commercial implementation of these systems are explored alongside an assessment of the current patent landscape.

The Hedgehog pathway and its inhibitors: Emerging therapeutic approaches for basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSC). Although surgery is the first-line treatment, BCC can lead in some cases, to a metastatic or advanced form, requiring targeted combination therapies. The Hedgehog (Hh) signalling pathway is the major pathway associated with the formation of basal carcinoma tumorigenesis, thus, targeting this is a promising therapeutic approach. Some Hh inhibitors have been approved by the US Food and Drug Administration (FDA), such as vismodegib and sonidegib. However, both of these showed limited effectiveness against resistant tumors. Therefore, an essential understanding of the mechanisms involved in the Hh signaling pathway is necessary to improve tumor inhibition.

Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives.

Numerous treatments are available for cancer, including chemotherapy, immunotherapy, radiation therapy, hormone therapy, biomarker testing, surgery, photodynamic therapy, etc. Photodynamic therapy (PDT) is an effective, non-invasive, novel, and clinically approved strategy to treat cancer. In PDT, three main agents are utilized, i.e., photosensitizer (PS) drug, oxygen, and light. At first, the photosensitizer is injected into blood circulation or applied topically, where it quickly becomes absorbed or accumulated at the tumor site passively or actively. Afterward, the tumor is irradiated with light which leads to the activation of the photosensitizing molecule. PS produces the reactive oxygen species (ROS), resulting in the death of the tumor cell. However, the effectiveness of PDT for tumor destruction is mainly dependent on the cellular uptake and water solubility of photosensitizer molecules. Therefore, the delivery of photosensitizer molecules to the tumor cell is essential in PDT against cancer. The non-specific distribution of photosensitizer results in unwanted side effects and unsuccessful therapeutic outcomes. Therefore, to improve PDT clinical outcomes, the current research is mostly focused on developing actively targeted photosensitizer molecules, which provide a high cellular uptake and high absorption capacity to the tumor site by overcoming the problem associated with conventional PDT. Therefore, this review aims to provide current knowledge on various types of actively and passively targeted organic and inorganic nanocarriers for different cancers.

Fluorescence-based method for sensitive and rapid estimation of chlorin e6 in stealth liposomes for photodynamic therapy against cancer.

Chlorin e6 is a chlorine-based porphyrin containing photosensitizer mainly used for the therapy in cancers like neck and head, early-stage lung cancer, and topical skin cancers. The present study provides a comprehensive account of a highly sensitive, precise, and validated method for the quantification of chlorin e6 in its liposomal formulation. This method is based on the systemic study of the fluorescence action of chlorin e6 in acetonitrile solvent. This experiment follows the analytical method validation parameters as per the International Conference on Harmonization (ICH). Chlorin e6 molecule exhibits strong fluorescence at a wavelength of emission 665 nm, upon excitation at a wavelength of excitation 400 nm in acetonitrile. The linearity of the fluorescence concentration plot was observed over a concentration range of 50 to 1000 ng/mL. The developed and validated method was successfully applied for the estimation of encapsulation efficiency in in-house developed stealth liposomes. Also, stock solution stability and photodegradation study of chlorin e6 were further conducted.

Nanocarrier Based Topical Drug Delivery- A Promising Strategy for Treatment of Skin Cancer.

Skin cancers are one of the most widespread and complex forms of the disease, resulting in very high mortality rates across the world. The current treatments available for skin cancer include chemotherapy, surgery, radiotherapy, etc. The selected treatment options for skin cancer are usually decided based on the condition of a patient and the type of skin cancer. The effectiveness of skin cancer therapy is still limited because of poor penetrability of the drug into stratum corneum or lesions, low efficacy, required higher concentration of the active pharmaceutical ingredients to reach a therapeutic effect. Besides, low bioavailability at the site of action, the requirement of high dose, causes skin irritation, which significantly hinders the drug absorption through the stratum corneum. Thus, nanocarriers have been used to bypass the problems associated with conventional anti-cancer drug delivery systems. In the current scenario, nanotechnology-based therapy has shown great potential in the management of skin cancer, and these can be used for a more efficient drug delivery system to treat cancers. In this review article, the information on different nanocarrier systems for skin cancer has been elucidated. Moreover, the various nanoparticulate strategies and their effectiveness to treat skin cancer have been discussed.

Recent avenues in Novel Patient-Friendly Techniques for the Treatment of Diabetes.

BACKGROUND: Diabetes is one of the most common chronic metabolic disorders which affect the quality of human life worldwide. As per the WHO report, between 1980 to 2014, the number of diabetes patients increases from 108 million to 422 million, with a global prevalence rate of 8.5% per year. Diabetes is the prime reason behind various other diseases like kidney failure, stroke, heart disorders, glaucoma, etc. It is recognized as the seventh leading cause of death throughout the world. The available therapies are painful (insulin injections) and inconvenient due to higher dosing frequency. Thus, to find out a promising and convenient treatment, extensive investigations are carried out globally by combining novel carrier system (like microparticle, microneedle, nanocarrier, microbeads etc.) and delivery devices (insulin pump, stimuli-responsive device, inhalation system, bioadhesive patch, insulin pen etc.) for more precise diagnosis and painless or less invasive treatment of disease. OBJECTIVE: The review article is made with an objective to compile information about various upcoming and existing modern technologies developed to provide greater patient compliance and reduce the undesirable side effect of the drug. These devices evade the necessity of daily insulin injection and offer a rapid onset of action, which sustained for a prolonged duration of time to achieve a better therapeutic effect. CONCLUSION: Despite numerous advantages, various commercialized approaches, like Afrezza (inhalation insulin) have been a failure in recent years. Such results call for more potential work to develop a promising system. The novel approaches range from the delivery of non-insulin blood glucose lowering agents to insulin-based therapy with minimal invasion are highly desirable.