ABSTRACT
Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.
Subject(s)
Drug Delivery Systems , Gels , Lecithins , Psoriasis , Thalidomide , Thalidomide/analogs & derivatives , Psoriasis/drug therapy , Lecithins/chemistry , Animals , Mice , Thalidomide/administration & dosage , Thalidomide/chemistry , Thalidomide/pharmacokinetics , Skin Absorption/drug effects , Skin/metabolism , Skin/drug effects , Administration, Cutaneous , Administration, Topical , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Drug Evaluation, Preclinical , Imiquimod/administration & dosage , MaleABSTRACT
Typically, antibody-drug conjugates (ADCs) are made up of a humanized antibody and a small-molecule medication connected by a chemical linker. ADCs' ability to deliver cytotoxic agents to the specific site with reduced side effects showed promising results in oncology. To date, fourteen ADCs have been approved by the US Food and Drug Administration, and approximately 297 ADCs are in pre-clinical/clinical stages in the oncology area. Inspired by these outcomes, a few scientists explored the potential of antibody-drug conjugates in non-oncological conditions such as arthritis, myasthenia gravis, immunological disorders, and kidney failure. However, there are limited data available on the non-oncological applications of antibody-drug conjugates. This current review focuses on the non-oncological applications of antibody-drug conjugates, their developmental studies, testing procedures, in vitro evaluations, and pre-clinical testing. Additionally, a summary of the restrictions, difficulties, and prospects for ADCs in non-oncological applications is provided.
ABSTRACT
BACKGROUND: Epilepsy is one of the major neurological disorders, affecting about 50 million people globally. Oral, intravenous, and rectal delivery systems are available for the management of epileptic seizures. However, intranasal delivery serves beneficial for delivering anti-epileptic drugs owing to the advantages it offers. OBJECTIVE: Various approaches have been developed over the years aiming to attain either a safer or faster brain delivery; a nasal delivery system proposes significant outcomes. The non-invasiveness and high vascularity contribute to the high permeability of the nasal mucosa, allowing rapid drug absorption. This review highlights some of the promising novel approaches delivering antiepileptic drugs efficiently employing the nasal route. METHODS: The method includes a collection of data from different search engines like PubMed, ScienceDirect, SciFinder for obtaining appropriate and relevant literature regarding epilepsy, intranasal delivery of antiepileptic agents, and novel therapeutics. RESULTS: The present review underlines the majority of work related to intranasal delivery in the treatment of epilepsy, aiming to draw the attention of the researchers towards the easiest and efficient ways of formulation for the delivery of antiepileptics during seizures. CONCLUSION: This review intends to provide understanding about the delivery aspects of anti-epileptic drugs, the benefits of intranasal delivery, and the novel approaches employed for the treatment of epilepsy.
