Abstract:34Although vital to the immune system, macrophages can act as reservoirs for 35 pathogens such as tuberculosis and human immunodeficiency virus. Limitations in the 36 treatment of such diseases include targeting therapeutics directly to macrophages and the 37 large systemic dosages needed. The objective of this study is to develop a nanoparticle 38 (NP)-based drug delivery system that can provide targeted delivery into macrophages. 39Acetalated dextran (Ac-Dex) NP loaded with the lipophilic model compound curc… Show more
“…This corroborated what has previously been reported, where addition of PS to PVA-coated dextran nanoparticles resulted in significant increases in both size and PDI, suggesting its presence on the surface of nanoparticles as an efficient coat. 47 Figure 1 Effect of addition of different concentrations of phosphatidyl serine (PS) or hyaluronate sodium solution on LNC colloidal properties. ( A and , C ) Particle size and polydispersity index (PDI); ( B and , D ) corresponding ζ-potential values.…”
Section: Resultsmentioning
confidence: 99%
“…This corroborated what has previously been reported, where addition of PS to PVA-coated dextran nanoparticles resulted in significant increases in both size and PDI, suggesting its presence on the surface of nanoparticles as an efficient coat. 47 Regarding ζ-potential data, Figure 1B shows that increasing PS concentration from 0 to 0.5% w/v resulted in an increase in corresponding negative ζ-potential from −15.8±3.1 to −50.2±1.6, respectively. This in turn further confirmed the efficient integration of PS into the shell of the LNCs.…”
Introduction:Liver fibrosis represents a serious global disease with no approved treatment. Tanshinone IIA (TSIIA) is a phytomedicine with documented activity in treating many hepatic disorders. TSIIA has been reported to have potent anti-inflammatory and antioxidant properties. It can also induce apoptosis for activated hepatic stellate cells, and is thereby considered as a promising herbal remedy for treating fibrotic liver. However, its poor aqueous solubility, short half-life, exposure to the first-pass effect, and low concentration reaching targeted cells constitute the major barriers hindering its effective therapeutic potential. Therefore, this work aimed at enhancing TSIIA systemic bioavailability together with achieving active targeting potential to fibrotic liver via its incorporation into novel modified lipid nanocapsules (LNCs). Methods: Blank and TSIIA-loaded LNCs modified with either hyaluronate sodium or phosphatidyl serine were successfully prepared, optimized, and characterized both in vitro and in vivo.
Results:The developed LNCs showed good colloidal properties (size ≤100 nm and PDI ≤0.2), high drug-entrapment efficiency (>97%) with sustained-release profile for 24 hours, high storage stability up to 6 months, and good in vitro serum stability. After a single intraperitoneal injection, the administered LNCs exhibited a 2.4-fold significant increase in AUC 0-∞ compared with the TSIIA suspension (p≤0.01). Biodistribution-study results proved the liver-targeting ability of the prepared modified LNCs, with a significant ~1.5-fold increase in hepatic accumulation compared with the unmodified formulation (p≤0.05). Moreover, the modified formulations had an improved antifibrotic effect compared with both unmodified LNCs and TSIIA suspension, as evidenced by the results of biochemical and histopathological evaluation.
Conclusion:The modified TSIIA-LNCs could be regarded as promising novel targeted nanomedicines for effective management of liver fibrosis.
“…This corroborated what has previously been reported, where addition of PS to PVA-coated dextran nanoparticles resulted in significant increases in both size and PDI, suggesting its presence on the surface of nanoparticles as an efficient coat. 47 Figure 1 Effect of addition of different concentrations of phosphatidyl serine (PS) or hyaluronate sodium solution on LNC colloidal properties. ( A and , C ) Particle size and polydispersity index (PDI); ( B and , D ) corresponding ζ-potential values.…”
Section: Resultsmentioning
confidence: 99%
“…This corroborated what has previously been reported, where addition of PS to PVA-coated dextran nanoparticles resulted in significant increases in both size and PDI, suggesting its presence on the surface of nanoparticles as an efficient coat. 47 Regarding ζ-potential data, Figure 1B shows that increasing PS concentration from 0 to 0.5% w/v resulted in an increase in corresponding negative ζ-potential from −15.8±3.1 to −50.2±1.6, respectively. This in turn further confirmed the efficient integration of PS into the shell of the LNCs.…”
Introduction:Liver fibrosis represents a serious global disease with no approved treatment. Tanshinone IIA (TSIIA) is a phytomedicine with documented activity in treating many hepatic disorders. TSIIA has been reported to have potent anti-inflammatory and antioxidant properties. It can also induce apoptosis for activated hepatic stellate cells, and is thereby considered as a promising herbal remedy for treating fibrotic liver. However, its poor aqueous solubility, short half-life, exposure to the first-pass effect, and low concentration reaching targeted cells constitute the major barriers hindering its effective therapeutic potential. Therefore, this work aimed at enhancing TSIIA systemic bioavailability together with achieving active targeting potential to fibrotic liver via its incorporation into novel modified lipid nanocapsules (LNCs). Methods: Blank and TSIIA-loaded LNCs modified with either hyaluronate sodium or phosphatidyl serine were successfully prepared, optimized, and characterized both in vitro and in vivo.
Results:The developed LNCs showed good colloidal properties (size ≤100 nm and PDI ≤0.2), high drug-entrapment efficiency (>97%) with sustained-release profile for 24 hours, high storage stability up to 6 months, and good in vitro serum stability. After a single intraperitoneal injection, the administered LNCs exhibited a 2.4-fold significant increase in AUC 0-∞ compared with the TSIIA suspension (p≤0.01). Biodistribution-study results proved the liver-targeting ability of the prepared modified LNCs, with a significant ~1.5-fold increase in hepatic accumulation compared with the unmodified formulation (p≤0.05). Moreover, the modified formulations had an improved antifibrotic effect compared with both unmodified LNCs and TSIIA suspension, as evidenced by the results of biochemical and histopathological evaluation.
Conclusion:The modified TSIIA-LNCs could be regarded as promising novel targeted nanomedicines for effective management of liver fibrosis.
“…Following intravenous administration of PS-microbubbles, ultrasound was used to decompose the particles from micro- to nano-sized, to facilitate penetration of the blood-brain barrier. In a similar study, acetylated dextran nanoparticles were coated with 1, 2-dipalmitoyl-sn-glycero-3-phospho-L-serine to promote the uptake of curcumin by macrophages ( Shah et al ., 2019 ). PS-coated dextran nanoparticles were taken up at a 4-fold higher rate by RAW 264.7 macrophages compared to control A549 lung cancer cells.…”
Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.
“… 25 , 26 , 27 Phosphatidylserine coatings have been previously employed to enhance the uptake of liposomal nanoparticles by macrophages. 28 , 29 Thus, our Nanotraps were further designed to guide the phosphatidylserine-specific phagocytosis by macrophages, enabling not only the containment but also the clearance of SARS-CoV-2 through binding and subsequent phagocytosis.…”
SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed “Nanotraps,” completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus
in vitro
. Furthermore, the Nanotraps demonstrated an excellent biosafety profile
in vitro
and
in vivo
. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an
ex vivo
lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
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