Unveiling the potential of ursolic acid modified hyaluronate nanoparticles for combination drug therapy in triple negative breast cancer.

Triple negative breast cancer (TNBC) represents the most aggressive and heterogenous disease, and combination therapy holds promising potential. Here, an enzyme-responsive polymeric prodrug with self-assembly properties was synthesized for targeted co-delivery of paclitaxel (PTX) and ursolic acid (UA). Hyaluronic acid (HA) was conjugated with UA, yielding an amphiphilic prodrug with 13.85 mol% UA and a CMC of 32.3 µg/mL. The HA-UA conjugate exhibited ∼14 % and 47 % hydrolysis at pH 7.4 and in tumor cell lysate. HA-UA/PTX NPs exhibited a spherical structure with 173 nm particle size, and 0.15 PDI. The nanoparticles showed high drug loading (11.58 %) and entrapment efficiency (76.87 %) of PTX. Release experiments revealed accelerated drug release (∼78 %) in the presence of hyaluronidase enzyme. Cellular uptake in MDA-MB-231 cells showed enhanced uptake of HA-UA/PTX NPs through CD44 receptor-mediated endocytosis. In vitro, HA-UA/PTX NPs exhibited higher cytotoxicity, apoptosis, and mitochondrial depolarization compared to PTX alone. In vivo, HA-UA/PTX NPs demonstrated improved pharmacokinetic properties, with 2.18, 2.40, and 2.35-fold higher AUC, t1/2, and MRT compared to free PTX. Notably, HA-UA/PTX NPs exhibited superior antitumor efficacy with a 90 % tumor inhibition rate in 4T1 tumor model and low systemic toxicity, showcasing their significant potential as carriers for TNBC combination therapy.

Harnessing the potential of fatty Acid-Surfactant-Based micellar gel for enhanced topical delivery of Apremilast in psoriasis treatment.

Apremilast (APR) is a potent anti-psoriatic agent that inhibits the phosphodiesterase 4 enzyme. Due to the poor oral bioavailability and associated systemic side effects the clinical applicability of APR has been constrained. Nanotechnology-based carrier system presents a novel option to increase the efficacy of the topical treatment of APR. The current investigation deals with the development of fatty acid-surfactant conjugate-based hybrid mixed micellar gel (HMMG) for the topical delivery of APR. The developed micelles exhibited an average size of 83.59 ± 4.46 nm, PDI of 0.239 ± 0.047, % entrapment efficiency of âˆ¼ 94.78 ± 3.98 %, with % practical drug loading of ∼11.37 ± 3.14 %. TEM analysis revealed the spherical shape of micelles. The hybrid micelles were further loaded in a carbopol®934P gel base for ease of application. Ex vivo permeation study revealed enhanced permeation and âˆ¼ 38-fold higher retention in deeper layers of skin from a hybrid micellar gel. In vivo, assessment demonstrated augmented efficacy of APR-HMMG as compared to 0.1 % betamethasone valerate. Also, APR-HMMG showed no sign of irritation, suggesting superior safety as a topical application. Thus, the proposed formulation strategy represents a viable avenue for enhancing the therapeutic efficacy of various anti-psoriatic moieties.

Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer's Disease Management.

Alzheimer's disease, a progressive neurodegenerative condition, is characterized by a gradual decline in cognitive functions. Current treatment approaches primarily involve the administration of medications through oral, parenteral, and transdermal routes, aiming to improve cognitive function and alleviate symptoms. However, these treatments face limitations, such as low bioavailability and inadequate permeation. Alternative invasive methods, while explored, often entail discomfort and require specialized assistance. Therefore, the development of a non-invasive and efficient delivery system is crucial. Intranasal delivery has emerged as a potential solution, although it is constrained by the unique conditions of the nasal cavity. An innovative approach involves the use of nano-carriers based on nanotechnology for intranasal delivery. This strategy has the potential to overcome current limitations by providing enhanced bioavailability, improved permeation, effective traversal of the blood-brain barrier, extended retention within the body, and precise targeting of the brain. The comprehensive review focuses on the advancements in designing various types of nano-carriers, including polymeric nanoparticles, metal nanoparticles, lipid nanoparticles, liposomes, nanoemulsions, Quantum dots, and dendrimers. These nano-carriers are specifically tailored for the intranasal delivery of therapeutic agents aimed at combatting Alzheimer's disease. In summary, the development and utilization of intranasal delivery systems based on nanotechnology show significant potential in surmounting the constraints of current Alzheimer's disease treatment strategies. Nevertheless, it is essential to acknowledge regulatory as well as toxicity concerns associated with this route; meticulous consideration is required when engineering a carrier. This comprehensive review underscores the potential to revolutionize Alzheimer's disease management and highlights the importance of addressing regulatory considerations for safe and effective implementations. Embracing this strategy could lead to substantial advancements in the field of Alzheimer's disease treatment.