Background: Pulsatile drug delivery of actives based on the body's biological rhythms came into sight as a novel and emerging concept in the field of drug delivery. The concept of late has given birth to another field of research worth exploring: multiple-pulse drug delivery.
Objective: Delivering a drug in multiple pulses has been applied to antibiotics for effective and patient compliant drug delivery. Delivering antibiotics in divided pulses results in better annihilation of microbes, as it prevents them going into a resistant/dormant stage and developing biological tolerance. The concept appears to have potential, and on 16 March 2009 MiddleBrook Pharmaceuticals, Inc. will launch the first of such once-daily product based on their proprietary pulsatile drug delivery technology, PULSYS.
Methods: This review focuses on the rationale, possible strategies and technologies employed for multiple-pulse delivery, as well as current status and future trends.
Conclusion: The concept is in its infancy and promises great potential in the fight against microbial resistance; many approved formulations based on similar approaches with new and improved therapeutic paradigms are anticipated in the near future.
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http://dx.doi.org/10.1517/17425240902895972 | DOI Listing |
J Med Chem
January 2025
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood-brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery.
View Article and Find Full Text PDFAnal Bioanal Chem
January 2025
Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China.
Extracellular vesicles (EVs) have been demonstrated to own the advantages in evading phagocytosis, crossing biological barriers, and possessing excellent biocompatibility and intrinsic stability. Based on these characteristics, EVs have been used as effective therapeutic carriers for drug delivery, but the low drug loading capacity greatly limits further applications. Herein, we developed a drug loading method based on cell-penetrating peptide (CPP) to enhance the encapsulation of therapeutic reagents in EVs, and EVs-based drug delivery system achieved higher killing efficacy to tumor cells.
View Article and Find Full Text PDFChemMedChem
January 2025
UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers, groupe « Systèmes Moléculaires Programmés », Faculté des Sciences Fondamentales et Appliquées, 4 rue Michel Brunet, TSA 51106, 86073, Poitiers, FRANCE.
The development of novel therapeutic strategies enabling the selective destruction of tumors while sparing healthy tissues is of great interest to improve the efficacy of cancer chemotherapy. In this context, we designed a β-glucuronidase-responsive albumin-binding prodrug programmed to release a potent Isocombretastatin A-4 analog within the tumor microenvironment. When injected at a non-toxic dose in mice bearing orthotopic triple-negative mammary tumors, this prodrug produced a significant anticancer activity, therefore offering a valuable alternative to the systemic administration of the parent drug.
View Article and Find Full Text PDFBiomater Sci
January 2025
Department of Urology, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Changsha, 410013, Hunan, China.
Gemcitabine (GEM) is a first line chemotherapy drug for bladder cancer (BCa). GEM's lack of specificity has led to disadvantages, resulting in low efficiency, especially when combined with the targeted treatment of BCa stem cells (CSCs), which is considered the cause of BCa recurrence and progression. To enhance the anti-cancer effect and reduce the side effects of GEM targeting of BCa cells/CSCs, an aptamer drug conjugate (ApDC) targeted delivery system was used to improve the efficiency of GEM in BCa therapy using EpCAM aptamer-GEM conjugates based on the epithelial cell adhesion molecule (EpCAM), which is highly expressed on the cell membrane of BCa cells/CSCs.
View Article and Find Full Text PDFComput Methods Biomech Biomed Engin
January 2025
Department of Clinical Surgery, Cty Clin Emergency Hosp, Sibiu, Romania.
This study examines heat transfer and nanofluid-enhanced blood flow behaviour in stenotic arteries under inflammatory conditions, addressing critical challenges in cardiovascular health. The blood, treated as a Newtonian fluid, is augmented with gold nanoparticles to improve thermal conductivity and support drug delivery applications. A hybrid methodology combining finite element method (FEM) for numerical modelling and artificial neural networks (ANN) for stability prediction provides a robust analytical framework.
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