Innovative Nanoparticulate Strategies in Colon Cancer Treatment: A Paradigm Shift.

As a major public health issue, colorectal cancer causes 9.4% of total cancer-related deaths and comprises 10% of new cancer diagnoses worldwide. In the year 2023, an estimated 153,020 people are expected to receive an identification of colorectal cancer (CRC), resulting in roughly 52,550 fatalities anticipated as a result of this illness. Among those impacted, approximately 19,550 cases and 3750 deaths are projected to occur in individuals under the age of 50. Irinotecan (IRN) is a compound derived from the chemical structure of camptothecin, a compound known for its action in inhibiting DNA topoisomerase I. It is employed in the treatment strategy for CRC therapies. Comprehensive in vivo and in vitro studies have robustly substantiated the anticancer efficacy of these compounds against colon cancer cell lines. Blending irinotecan in conjunction with other therapeutic cancer agents such as oxaliplatin, imiquimod, and 5 fluorouracil enhanced cytotoxicity and improved chemotherapeutic efficacy. Nevertheless, it is linked to certain serious complications and side effects. Utilizing nano-formulated prodrugs within "all-in-one" carrier-free self-assemblies presents an effective method to modify the pharmacokinetics and safety portfolio of cytotoxic chemotherapeutics. This review focuses on elucidating the mechanism of action, exploring synergistic effects, and innovating novel delivery approaches to enhance the therapeutic efficacy of irinotecan.

Revamping the corneal permeability and antiglaucoma therapeutic potential of brinzolamide using transniosomes: optimization, in vitro and preclinical evaluation.

Aim: This study aims to explore potential of transniosomes, a hybrid vesicular system, as ocular drug-delivery vehicle. Materials & methods: Thin-film hydration technique was used to fabricate brinzolamide-loaded transniosomes (BRZ-TN) and optimized using Box-Behnken design, further exhaustively characterized for physicochemical evaluations, deformability, drug release, permeation and preclinical evaluations for antiglaucoma activity. Results: The BRZ-TN showed ultradeformability (deformability index: 5.71), exhibiting sustained drug release without irritation (irritancy score: 0) and high permeability compared with the marketed formulation or free drug suspension. The extensive in vivo investigations affirmed effective targeted delivery of transniosomes, with brinzolamide reducing intraocular pressure potentially. Conclusion: Our findings anticipated that BRZ-TN is a promising therapeutic nanocarrier for effectively delivering cargo to targeted sites by crossing corneal barriers.

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Nanocrystal technologies in biomedical science: From the bench to the clinic.

The pharmaceutical industry is grappling with a pressing crisis in drug development characterized by soaring R&D costs, setbacks in blockbuster drug development due to poor aqueous solubility, and patent-related limitations on newly approved molecules. To combat these challenges, diverse strategies have emerged to enhance the solubility and dissolution rates of Biopharmaceutics Classification System (BCS) II and IV drug molecules. Enter drug nanocrystals, a revolutionary nanotechnology-driven, carrier-free colloidal drug delivery system. This review provides a comprehensive insight into nanocrystal strategies, stabilizer selection criteria, preparation methods, advanced characterization techniques, the evolving nanocrystal technological landscape, current market options, and exciting clinical prospects for reshaping the future of pharmaceuticals.

Hyaluronic acid-engineered Bcl-2 inhibitor nanocrystals for site-specific delivery to breast tumor cells.

Aim: This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. Materials & methods: An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of in vitro drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. Results: HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive in vitro cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (IC50: 2.00 µg/ml) compared with VEN-NCs. Conclusion: Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.

Exploring Penetration Ability of Carbonic Anhydrase Inhibitor-Loaded Ultradeformable Bilosome for Effective Ocular Application.

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04 nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10 h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6 h and trans-corneal permeability of 8.78 ± 0.14 cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.

Recent trends and updates on ultradeformable and elastic vesicles in ocular drug delivery.

Ocular drug delivery is enigmatic on account of various physiological precorneal barriers that ultimately hinder efficient drug penetration and corneal absorption. Ultradeformable vesicles embody non-ionic surfactants, edge activators and vesicular builders that provide enormous elasticity and deformability. The elastic vesicles can cross the ocular barriers owing to their peculiar squeezability and distorting ability and, thus, establish an infallible shot for ocular delivery. This review provides an overview of the recent advancements and updates of elastic vesicles as effective ocular drug delivery vehicles.

Preparation and Evaluation of Modified Chitosan Nanoparticles Using Anionic Sodium Alginate Polymer for Treatment of Ocular Disease.

Mucoadhesive nanoparticles offer prolonged drug residence time at the corneal epithelium by adhering to the mucous layer of the eye. Here, in this research investigation, voriconazole-loaded chitosan mucoadhesive nanoparticles (VCZ-MA-NPs) were modified to mucous-penetrating nanoparticles (VCZ-MP-NPs) by coating them with anionic polymer sodium alginate. The ionic gelation method was utilized to prepare mucoadhesive chitosan nanoparticles, which were further coated with sodium alginate to obtain the surface properties essential for mucous penetration. The developed VCZ-MA-NPs and VCZ-MP-NPs were evaluated extensively for physicochemical delineation, as well as in vitro and ex vivo studies. The particle size, polydispersity index, and ζ potential of the VCZ-MA-NPs were discovered to be 116 ± 2 nm, 0.23 ± 0.004, and +16.3 ± 0.9 mV, while the equivalent values for VCZ-MP-NPs were 185 ± 1 nm, 0.20 ± 0.01, and -24 ± 0.9 mV, respectively. The entrapment efficiency and drug loading were obtained as 88.06%±1.29% and 7.27% ± 0.95% for VCZ-MA-NPs and 91.31% ± 1.05% and 10.38% ± 0.87% for VCZ-MP-NPs, respectively. The formulations were found to be stable under different conditions (4 °C, 25 °C, and 40 °C). Chitosan nanoparticles and modified nanoparticles showed a spherical and smooth morphology under electron microscopic imaging. An excised caprine cornea was used for the ex vivo permeation study, exhibiting 58.98% ± 0.54% and 70.02% ± 0.61% drug permeation for VCZ-MA-NPs and VCZ-MP-NPs, respectively. The findings revealed that the mucous-penetrating nanoparticles could effectively pass through the corneal epithelium, thus overcoming the mucous barrier and fungal layer of the eye, which highlights their potential in the treatment of fungal keratitis.