Transethosome as a versatile nano vehicle for various indications and its regulatory insights.

Transethosomes, classified as 3rd generation nanocarriers, have gained global acclaim due to their profound potential in addressing diverse medical conditions. Their superior dermal penetration, attributed to essential constituents, such as edge activators and alcohol, sets them apart from other nanoformulations. The current review article embarks with an introduction followed by a comprehensive exploration of transethosome structures, differentiating them from fellow nanocarriers. A detailed analysis of characteristics and the spectrum of marketed products of various nanocarriers is also provided. Furthermore, the article offers a taxonomy of preparation methods of transethosomes and reports the frequently employed methods. It briefly surveys research studies encompassing various drug categories, spanning a wide range of medical conditions. In summary, this review article is dedicated to achieving several pivotal aims and objectives. We aim to substantiate the superior attributes of transethosomes when compared to conventional commercial products and other nanoformulations, demonstrating their clinical promise in addressing various human medical conditions. Additionally, we seek to elucidate the regulatory pathway required to secure approvals for transethosomes from relevant regulatory authorities and shine a light on their innovative potential as revealed in patent literature. Collectively, these objectives contribute to a comprehensive understanding of the significance and potential of transethosomes in the field of pharmaceutical nanotechnology.

Regulatory landscape and challenges in CAR-T cell therapy development in the US, EU, Japan, and India.

Chimeric Antigen Receptor-T cell (CAR-T) therapy has evolved as a revolutionary cancer treatment modality, offering remarkable clinical responses by harnessing the power of a patient's immune system to target and eliminate cancer cells. However, the development and commercialization of CAR-T cell therapies are accompanied by complex regulatory requirements and challenges. This therapy falls under the regulatory category of advanced therapy medicinal products. The regulatory framework and approval tools of regenerative medicine, especially CAR-T cell therapies, vary globally. The present work comprehensively analyses the regulatory landscape and challenges in CAR-T cell therapy development in four key regions: the United States, the European Union, Japan, and India. This work explores the unique requirements and considerations for preclinical studies, clinical trial design, manufacturing standards, safety evaluation, and post-marketing surveillance in each jurisdiction. Due to their complex nature, developers and manufacturers face several challenges. In India, despite advancements in treatment protocols and government-sponsorships, there are still several difficulties regarding access to treatment for the increasing number of cancer patients. However, India's first indigenously developed CAR-T cell therapy, NexCAR19, for B-cell lymphoma or leukemia, approved and available at a low cost compared to other available CAR-T therapies, raises great hope in the battle against cancer. Several strategies are proposed to address the identified hurdles from global and Indian perspectives. It discusses the benefits of aligning regulatory requirements across regions, eventually facilitating international development and enabling access to this transformative therapy.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.

Photoresponsive liposomes: an alternative of ELISA for the detection of low quantities of target substances.

Photoresponsive liposome development is needed to serve as a facile alternative to ELISA which is ineffective for detecting small levels of biomarkers due to low detection sensitivity. The US20210396744 patent application outlines novel photoresponsive liposomes for the detection of target substances with the aid of light. Although versatile, there may be possible stability issues that can be avoided with the appropriate selection of liposome components. Furthermore, the clinical success of this technology depends on many parameters like plasma stability, efficient loading of photosensitive components in the membrane and immobilization of molecular recognition elements to the membrane. Despite several challenges, they possess enormous potential to become a non-invasive tool for the detection of target substances.

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update.

Dwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.

Prominence of bioresponsive DNA nanococoons in tackling post-surgery cancer recurrence.

Post-surgery cancer recurrence is one of the reasons for increased cancer cases. The effective usage of the enhanced permeability and retention effect of a nanocarrier infused with the bioresponsive release mechanism of checkpoint inhibitors (aPD1 and aCTLA4) can become a boon to mankind. DNA nanococoons (DNCs) comprising cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) with potent immunostimulatory effects can significantly enhance anti-cancer activity. Triglycerylmonostearate (TGMS) with enzymatic cleavage potential at the wound sites of tumor resection, upon caging with restriction enzyme (HhaI) followed by attaching to DNCs, makes the immunotherapy bioresponsive. Hhal-TGMS-DNCs-aPD1 triggered by the inflammation at the wound site undergoes enzymatic cleavage, releases the restriction enzyme, converts DNCs to CpG ODNs sequentially and with sustained aPD1 release exerts an appreciable anti-cancer effect.

Paradigm of lyotropic liquid crystals in tissue regeneration.

The liquid crystalline phase has attracted tremendous attention from researchers across the globe due to its intriguing properties. In this article, we enumerate the different classes of liquid crystals. Lyotropic liquid crystals (LLCs) exhibit their liquid crystalline nature based on the surrounding solvent media, which opens novel horizons in drug delivery and tissue regeneration. The advantages of LLCs in the said fields and the thermodynamic mechanistic insights responsible for their structural stabilization have been conveyed. Various fabrication and characterization techniques, along with factors influencing the formation of LLCs, have been discussed. Applications in novel therapeutic avenues like bone extracellular matrix, cardiac remodeling, wound management, and implants have been unveiled. Also, regulatory considerations, patent, and clinical portfolios to circumvent the hurdles of clinical translation have been discussed. LLCs could be a promising approach in diverse avenues of tissue regeneration.

Lipid-based mesoporous silica nanoparticles: a paradigm shift in management of pancreatic cancer.

Pancreatic adenocarcinoma, a devastating disease, has the worst cancer prognosis in humans. It often develops resistance to common chemotherapy medications, such as gemcitabine, taxol and 5-fluorouracil. The dense stroma limits therapeutic efficacy in treating this disease. Low or limited drug loading capacity is another problem with current chemotherapeutic agents. There is a need to develop novel approaches to overcome these issues. Hence, an innovative approach has been proposed to co-deliver both hydrophilic (Gemcitabine) and hydrophobic (Paclitaxel) drugs in a single carrier using lipid bilayer-mesoporous silica nanoparticles (LB-MSNP). MSNPs offer effective drug delivery due to their superior bioavailability and physicochemical properties. Further, in order to achieve clinical translation and regulatory approval, toxicity and biodegradability of MSNPs must be resolved.

Highly stable, non-toxic and functionalized nanoemulsion for the early diagnosis and amelioration of cancer.

Aim: To overcome the limitations associated with conventional formulations for cancer treatment by the effective utilization of nanoemulsion with therapy and diagnosis through the single unit. Patent: US20210275687 describes the usage of functionalized various oil-in-water nanoemulsions as pharmacological vehicles with theranostic potential in cancer treatment. Materials & methods: Vitamin E, oleic acid, sphingomyelin, ligands for functionalization, contrast agents and therapeutic biomolecules. Results: The toxicity studies conducted on healthy mice did not show any apparent toxicity issues. The stability studies conducted at 40 °C and 75% relative humidity, which is mandatory for regulatory approval, indicated the adequate physical stability of the formulation. Conclusion: The studies exhibited the promising theranostic potential of the developed nanoemulsion for the effective management and diagnosis of cancer and metastatic diseases.

Sustained drug delivery strategies for treatment of common substance use disorders: Promises and challenges.

Substance use disorders (SUDs) are a leading cause of death and other ill health effects in the United States and other countries in the world. Several approaches ranging from detoxification, behavioral therapy, and the use of antagonists or drugs with counter effects are currently being applied for its management. Amongst these, drug therapy is the mainstay for some drug abuse incidences, as is in place specifically for opioid abuse or alcohol dependence. The severity of the havocs observed with the SUDs has triggered constant interest in the discovery and development of novel medications as well as suitable or most appropriate methods for the delivery of these agents. The chronic need of such drugs in users warrants the need for their prolonged or sustained systemic availability. Further, the need to improve patient tolerance to medication, limit invasive drug use and overall treatment outcome are pertinent considerations for embracing sustained release designs for medications used in managing SUDs. This review aims to provide an overview on up-to-date advances made with regards to sustained delivery systems for the drugs for treatment of different types of SUDs such as opioid, alcohol, tobacco, cocaine, and cannabis use disorders. The clinical relevance, promises and the limitations of deployed sustained release approaches along with future opportunities are discussed.