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Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel.

ABSTRACT: Most biopharmaceutics classification system (BCS) class IV drugs, with poor solubility and inferior permeability, are also substrates of P-glycoprotein (P-gp) and cytochrome P450 (CYP450), leading to their low oral bioavailability. The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles (PLHNs) to enhance the oral absorption of BCS IV drugs. In this paper, taking paclitaxel (PTX) as a drug model, PTX-loaded PLHNs were prepared by a self-assembly method. Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability. Three P-gp inhibitors (D-α-tocopherol polyethylene glycol 1000 succinate, pluronic P123 and Solutol^Ⓡ HS15) were incorporated into selected PLHNs, and a CYP450 inhibitor (the extract of VBRB, BC0) was utilized to jointly promote the drug absorption. Properties of all the PLHNs were characterized systemically, including particle size, zeta potential, encapsulation efficiency, morphology, stability, in vitro drug release, mucoadhesion, in situ intestinal permeability and in vivo systemic exposure. It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested, with absolute bioavailability 21.95%. P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%, 8-fold increase compared with that of PTX itself (4.75%). Taken together, our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption, especially for BCS IV drugs.

SUBMITTER: Qin L

PROVIDER: S-EPMC8261254 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD.

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| S-EPMC6122632 | biostudies-literature

Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing.

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| S-EPMC4077924 | biostudies-literature

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| S-EPMC4198073 | biostudies-literature

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| S-EPMC5604569 | biostudies-literature

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| S-EPMC6215448 | biostudies-literature

Lipid Polymer Hybrid Nanomaterials for mRNA Delivery.

Project description:IntroductionIn the past decade, messenger RNA (mRNA) has been extensively explored in a wide variety of biomedical applications. However, efficient delivery of mRNA is still one of the key challenges for its broad applications in the clinic. Recently, lipid polymer hybrid nanoparticles (LPNs) are evolving as a promising class of biomaterials for RNA delivery, which integrate the physicochemical properties of both lipids and polymers. We previously developed an N1,N3,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived lipid-like nanomaterial (TT3-LLN) which was capable of effectively delivering multiple types of mRNA. In order to further improve the delivery efficiency of TT3-LLN, in this study, we focused on studying the effects of incorporating different polymers on establishing LPNs and aimed to develop an optimized lipid polymer hybrid nanomaterial for efficient mRNA delivery.MethodsWe incorporated a series of biodegradable and biocompatible polymer materials into the formulation of TT3-LLNs to develop LPNs. mRNA delivery efficiency of different LPNs were evaluated and a systematic orthogonal optimization was further carried out.ResultsOur data indicate that PLGA4 (MW 24,000-38,000 g/mol) dramatically increased delivery efficiency of TT3-LLNs in comparison to other polymers. Further optimization identified PLGA4-7 LPNs (PLGA:mRNA=9:1, mass ratio; TT3:DOPE:Cholesterol:DMG-PEG2000=25:25:45:0.75, molar ratio) as a lead formulation, which displayed significantly enhanced delivery of two types of mRNA in three different human cell lines as compared with TT3-LLNs.ConclusionsResults from this study potentially provide new insights into developing LPNs for mRNA based therapeutics.

| S-EPMC6291228 | biostudies-literature

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| S-EPMC9364311 | biostudies-literature

Polymer-lipid hybrid nanoparticles as potential lipophilic anticancer drug carriers.

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| S-EPMC10504175 | biostudies-literature

Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells.

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| S-EPMC6452044 | biostudies-literature

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