Recent Advances in Drug Delivery and Formulation - Volume 19, Issue 1, 2025

Rheumatoid Arthritis is one of the most common auto-immune diseases that cause inflammation. It is characterized by pain, stiffness, tenderness, and swelling in joints, which may even lead to heart, lungs, or brain-related problems where age is the major factor involved, as around 55% older adults have been affected by it. Treatments including non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) etc., that are modified and formulated as nanocarriers for enhanced bioavailability, majorly aim at enhancing the rate and extent of drug reaching the bloodstream such as solid-lipid nanoparticles, liposomes, polymeric-micelles, polymeric nanoparticles etc. are used in the management of rheumatoid arthritis.

The following tools (Pubmed, Scopus, Google search engine, Google Scholar, Medline Search Engine, Elsevier) were used in the literature search.

Through the literature review, the development of nanocarrier shows a promising approach in the management of rheumatoid arthritis as compared to the conventional drug treatment such as biologic agents and non-steroidal anti-inflammatory drugs etc.

Rheumatoid Arthritis is a condition that occurs when the immune system, which normally helps to protect the body from infection and disease, attacks its own tissues. The disease causes pain, swelling as well as loss of function in joints. Therefore, life-long management is required by reducing the dose frequency and dosage regimen, which can be effectively approached by the development of a nano-carrier for significant drug uptake and low toxicity.

Chitosan is a biocompatible, mucoadhesive, and biodegradable polymer widely used for various purposes due to its biological activity and safety. The current study aimed to formulate Chitosan microspheres and conduct an in-vitro evaluation of their cytotoxicity. The concept is focused on targeted gut delivery and biological activities in gut microbiota remodelling.

The formulations were comprehensively characterized, encompassing SEM for surface morphology, particle size analysis, and FT-IR for structural understanding. Along with biological activity and cytotoxicity studies, dissolution efficiency was considered to understand release kinetics potential and accelerated stability studies to predict formulation shelf-life.

The formulation showed smooth spherical surface morphology with an average size range of 30.0 ± 5.0 µm and a charge of 20.35 ± 0.35 mV. Further, functional and thermal properties were determined using FT-IR and DSC, respectively. The microspheres showed a potent prebiotic potential in gut flora isolated and processed from a faecal sample of Wistar rats with prolonged release characteristics in the dissolution study. A cytotoxicity study using rat intestinal epithelial cells (IEC6) indicated that 40 mg /kg of microspheres could be considered an optimal dose for an in-vivo study.

The formulation demonstrated promising pharmaceutical applicability due to its potential prebiotic nature and slow release into the gut environment. After a thorough in vivo study, the microspheres can be broadly used to restore gut dysbiosis due to their potential prebiotic activities in various diseases and disorders, including but not limited to obesity, type-2 diabetes, cardiometabolic disease, and non-alcoholic fatty liver disease.

Genistein (GEN) shows significant anticancer potential, particularly against prostate cancer. However, its clinical application is limited by poor water solubility, rapid metabolism and excretion, low bioavailability, and lack of targeted delivery to cancer cells, hindering its effectiveness as a chemopreventive or therapeutic agent.

In this study, poly-ε-caprolactone (PCL) nanoparticles incorporating polyvinyl alcohol (PVA) as a stabilizer were engineered to encapsulate genistein (GEN) effectively. Utilizing a Quality by Design (QbD) methodology, the development and optimization of these nanoparticles were systematically approached.

GEN-loaded PCL nanoparticles (NPs) were prepared using the Solvent Evaporation Technique, ideal for encapsulating hydrophobic drugs. A Plackett–Burman design (PBD) identified key factors, followed by a Box–Behnken design (BBD) to optimize nanoparticle quality. The NPs were evaluated for particle size, zeta potential (ZP), polydispersity index (PDI), morphology, encapsulation efficiency (EE), in vitro drug release, and cytotoxicity.

The optimized formulation containing PCL, PVA, and Volume of organic solvent as 43.7 mg, 6.2 mg, and 10.0 ml, respectively was chosen because it showed EE (%) of 94.0%, average particle size of 150 nm, PDI of 0.10, ZP of -28.0 and exhibited sustained release of GEN for around four days. The antiproliferative activities of GEN PCL NPs were confirmed by the MTT test in vitro on malignant prostate carcinoma cell lines (PC3). Flow cytometric analysis showed that the inhibition of cell proliferation of more potent GEN PCL NPs is comparable with the effects of free GEN.

The findings indicate that genistein-loaded PCL nanoparticles have the potential to augment the anticancer efficacy of genistein, both in vitro and in vivo. This suggests their promise as a viable candidate for prostate cancer treatment.

Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients.

Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, in vitro GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An in vivo study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups.

Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7.

These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.