Title : Enhancing delivery of biopharmaceutics classification system class ii drugs through a novel carrageenan-alginate-oleogel matrix: A case study on praziquantel for improved therapeutic efficacy
Abstract:
Schistosomiasis, a waterborne neglected tropical disease (NTD) prevalent in sub-Saharan Africa and South-East Asia significantly impacts socio-economic development. Praziquantel (PZQ) serves as the primary treatment, effective against all human schistosome species. However, PZQ's bitter taste, lipophilicity, and substantial first-pass metabolism post-oral administration result in low patient compliance and requires high dosages for efficacy. Additionally, while effective against adult worms, PZQ is limited in treating juvenile worms, which then contribute to ongoing disease transmission and re-infection. Furthermore, the exclusive reliance on a single therapeutic agent for a disease with high morbidity and mortality raises concerns, and the potential emergence of resistance without an alternative drug could lead to severe consequences. Despite this severity, the current treatment options for this NTD remain limited. The limitations associated with PZQ drive the motivation behind this research effort, with the aim to develop an innovative drug delivery system using κ-carrageenan (κ-CG), alginate (AG), and oleogel to enhance the efficacy of PZQ. These components are selected for their unique mechanical properties and advantages in drug delivery systems. AG, a naturally occurring linear polysaccharide extracted from brown seaweed, is biocompatible, non-toxic, and water-soluble. It has demonstrated promise in targeted drug delivery, especially in the intestines, owing to its potential to shield the drug from the harsh conditions of the stomach in the gastrointestinal tract. κ-CG is a natural polysaccharide extracted from red seaweed and exhibits excellent gel properties. The incorporation of a drug-loaded oleogel (DLO) into the matrix will serve as a drug reservoir, improving intestinal absorption of PZQ. This study leverages the AG/κ-CG matrix to protect the drug-loaded oleogel within the harsh acidic stomach environment, where it will form a protective gel during its passage through the GI tract. As it progresses into the intestinal environment with a more neutral and alkaline pH, which is the preferable site for drug absorption, the AG/κ-CG matrix will dissolve, gradually exposing the drug-loaded oleogel. In the presence of bile salts and lipase enzymes, the oleogel will undergo breakdown, leading to the sustained release of the drug at the preferred absorption site. This innovative approach aims to enhance drug bioavailability, potentially reducing the required dosage. The study will explore the ternary matrix formulation by conducting a comprehensive analysis of the structural and physical properties of the material contained within this matrix. This in-depth investigation is crucial for our goal of achieving sustained release in the intestines. To gain an understanding of the physical and structural properties of the materials within the matrix, this study will employ various analytical techniques for the characterisation of the material. These include the use of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for investigating thermal behaviour, confocal light microscopy for qualitative observations of material morphology, Fourier-transform infrared spectroscopy (FTIR) to understand breakdown mechanisms through band appearance and disappearance, high-performance liquid chromatography (HPLC) for quantifying release material concentration, and a texture analyser for determining the Young modulus, which quantifies material elasticity and rigidity. Furthermore, we will examine the release kinetics through dissolution studies using the United States Pharmacopeia 2 paddle method. In addressing the limitations of PZQ and enhancing its drug delivery, this study holds promise for advancements in drug delivery strategies. In the context of NTDs, nanoparticulate systems offer a unique therapeutic alternative by improving existing drugs and enabling modified release for improved efficacy, minimal side effects, patient compliance and overall performance. The significance of this study, however, is not limited to NTDs; its applications can extend to broader pharmaceutical applications, enriching the expanding realm of knowledge in drug delivery systems and paving innovative paths for effective drug administration.
