The function of many membrane-enclosed intracellular structures relies on release of diffusing particles that exit through narrow pores or channels in the membrane. The rate of release varies with pore size, density, and length of the channel. We propose a simple approximate model, validated with stochastic simulations, for estimating the effective release rate from cylinders, and other simple-shaped domains, as a function of channel parameters. The results demonstrate that, for very small pores, a low density of channels scattered over the boundary is sufficient to achieve substantial rates of particle release. Furthermore, we show that increasing the length of passive channels will both reduce release rates and lead to a less steep dependence on channel density. Our results are compared to previously-measured local calcium release rates from tubules of the endoplasmic reticulum, providing an estimate of the relevant channel density responsible for the observed calcium efflux.
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http://dx.doi.org/10.1088/1478-3975/acb1ea | DOI Listing |
Pharmaceutics
December 2024
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA.
This study evaluates the efficacy of twin screw melt granulation (TSMG), and hot-melt extrusion (HME) techniques in enhancing the solubility and dissolution of simvastatin (SIM), a poorly water-soluble drug with low bioavailability. Additionally, the study explores the impact of binary polymer blends on the drug's miscibility, solubility, and in vitro release profile. SIM was processed with various polymeric combinations at a 30% / drug load, and a 1:1 ratio of binary polymer blends, including Soluplus (SOP), Kollidon K12 (K12), Kollidon VA64 (KVA), and Kollicoat IR (KIR).
View Article and Find Full Text PDFPharmaceutics
December 2024
College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang 10326, Republic of Korea.
Background/objectives: A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and duration of drug exposure.
Methods: Fenofibrate-loaded solid dispersions (FNSDs) were prepared using poloxamer 407 and Eudragit RSPO at varied ratios via solvent evaporation.
Pharmaceutics
December 2024
Department of Physico-Chemistry, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universității Street, 700115 Iasi, Romania.
Diabetes is a growing global health crisis that requires effective therapeutic strategies to optimize treatment outcomes. This study aims to address this challenge by developing and characterizing extended-release polymeric matrix tablets containing metformin hydrochloride (M-HCl), a first-line treatment for type 2 diabetes, and honokiol (HNK), a bioactive compound with potential therapeutic benefits. The objective is to enhance glycemic control and overall therapeutic outcomes through an innovative dual-drug delivery system.
View Article and Find Full Text PDFPharmaceutics
December 2024
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China.
Background: The clinical efficacies of anticancer drugs are limited by non-selective toxic effects on healthy tissues and low bioavailability in tumor tissue. Therefore, the development of vehicles that can selectively deliver and release drugs at the tumor site is critical for further improvements in patient survival.
Methods: We prepared a CEC nano-drug delivery system, CEC@ZIF-8, with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR).
Pharmaceutics
December 2024
Department of Pharmacology, Faculty of Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.
Background: Lipid vesicles, especially those utilizing biocompatible materials like chitosan (CHIT), hold significant promise for enhancing the stability and release characteristics of drugs such as indomethacin (IND), effectively overcoming the drawbacks associated with conventional drug formulations.
Objectives: This study seeks to develop and characterize novel lipid vesicles composed of phosphatidylcholine and CHIT that encapsulate indomethacin (IND-ves), as well as to evaluate their in vitro hemocompatibility.
Methods: The systems encapsulating IND were prepared using a molecular droplet self-assembly technique, involving the dissolution of lipids, cholesterol, and indomethacin in ethanol, followed by sonication and the gradual incorporation of a CHIT solution to form stable vesicular structures.
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