scholarly journals Synthesis and Characterization of pH-Sensitive Inulin Conjugate of Isoniazid for Monocyte-Targeted Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 555 ◽  
Author(s):  
Franklin Afinjuomo ◽  
Thomas G. Barclay ◽  
Ankit Parikh ◽  
Rosa Chung ◽  
Yunmei Song ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
Ph Sensitive ◽  
Proton Nuclear Magnetic Resonance ◽  
Antitubercular Drugs ◽  
Intracellular Targeting ◽  
Intracellular Drug Delivery ◽  
Uptake Studies ◽  
Endocytic Compartments

The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment.

scholarly journals Design and Characterization of Inulin Conjugate for Improved Intracellular and Targeted Delivery of Pyrazinoic Acid to Monocytes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 243 ◽  
Author(s):  
Franklin Afinjuomo ◽  
Thomas G. Barclay ◽  
Ankit Parikh ◽  
Yunmei Song ◽  
Rosa Chung ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
In Vitro Release ◽  
Amide Bond ◽  
Proton Nuclear Magnetic Resonance ◽  
Order Kinetic ◽  
Scanning Calorimetry ◽  
Intracellular Drug Delivery ◽  
Pyrazinoic Acid

The propensity of monocytes to migrate into sites of mycobacterium tuberculosis (TB) infection and then become infected themselves makes them potential targets for delivery of drugs intracellularly to the tubercle bacilli reservoir. Conventional TB drugs are less effective because of poor intracellular delivery to this bacterial sanctuary. This study highlights the potential of using semicrystalline delta inulin particles that are readily internalised by monocytes for a monocyte-based drug delivery system. Pyrazinoic acid was successfully attached covalently to the delta inulin particles via a labile linker. The formation of new conjugate and amide bond was confirmed using zeta potential, Proton Nuclear Magnetic Resonance (1HNMR) and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) confirmed that no significant change in size after conjugation which is an important parameter for monocyte targeting. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to establish the change in thermal properties. The analysis of in-vitro release demonstrated pH-triggered drug cleavage off the delta inulin particles that followed a first-order kinetic process. The efficient targeting ability of the conjugate for RAW 264.7 monocytic cells was supported by cellular uptake studies. Overall, our finding confirmed that semicrystalline delta inulin particles (MPI) can be modified covalently with drugs and such conjugates allow intracellular drug delivery and uptake into monocytes, making this system potentially useful for the treatment of TB.

Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar
Keyword(s):  
Cancer Cells ◽  
Cellular Uptake ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Curcumin Nanoparticles ◽  
Cytotoxicity Studies ◽  
Delivery Technique ◽  
Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

scholarly journals In Vitro Cellular Uptake Studies of Self-Assembled Fluorinated Nanoparticles Labelled with Antibodies

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1906
Author(s):  
Mona Atabakhshi-Kashi ◽  
Mónica Carril ◽  
Hossein Mahdavi ◽  
Wolfgang J. Parak ◽  
Carolina Carrillo-Carrion ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cellular Uptake ◽  
Hydrophobic Interactions ◽  
Intrinsic Properties ◽  
Wide Range ◽  
Self Assembled ◽  
Uptake Studies ◽  
Targeting Ability ◽  
Fluorinated Nanoparticles

Nanoparticles (NPs) functionalized with antibodies (Abs) on their surface are used in a wide range of bioapplications. Whereas the attachment of antibodies to single NPs to trigger the internalization in cells via receptor-mediated endocytosis has been widely studied, the conjugation of antibodies to larger NP assemblies has been much less explored. Taking into account that NP assemblies may be advantageous for some specific applications, the possibility of incorporating targeting ligands is quite important. Herein, we performed the effective conjugation of antibodies onto a fluorescent NP assembly, which consisted of fluorinated Quantum Dots (QD) self-assembled through fluorine–fluorine hydrophobic interactions. Cellular uptake studies by confocal microscopy and flow cytometry revealed that the NP assembly underwent the same uptake procedure as individual NPs; that is, the antibodies retained their targeting ability once attached to the nanoassembly, and the NP assembly preserved its intrinsic properties (i.e., fluorescence in the case of QD nanoassembly).

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

scholarly journals pH Sensitive Lipid-Polymer Hybrid Nanoparticles Mediated Delivery of Docetaxel: A Viable Approach for Breast Cancer Therapeutic Intervention Development

2020 ◽  
Author(s):  
Ye Yuan ◽  
Jia-Xing Song ◽  
Mei-Na Zhang ◽  
Baoshan Yuan
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Intervention Development ◽  
Ph Sensitive ◽  
Therapeutic Interventions ◽  
Hybrid Nanoparticles ◽  
Breast Cancer Cell Lines ◽  
Polymer Hybrid

Abstract Present study was planned for the development of pH sensitive lipid polymer hybrid nanoparticles (pHS-LPHNPs) loaded with docetaxel (DTX) for guided and target specific cytosolic-delivery delivery of docetaxel (DTX). pHS-LPHNPs were formulated to entrap DTX by self-assembled nano-precipitation technique and characterised with respect to zeta potential, particle-size, entrapment efficiency, PDI as well as invitro drug release. The cell viability, apoptosis, cellular-uptake, pharmacokinetics, bio-distribution in vital organs, % changes in tumour volume and survival of breast cancer bearing animals were used for the evaluation of efficacy of the formulation. In-vitro studies showed increased cytotoxicity at lower IC50 and better cellular-uptake of pHS-LPHNPs mediated drug by breast cancer cell lines. We saw the better rate of apoptosis of breast cancer cells via Annexin V/Propidium iodide staining. Moreover, in-vivo studies demonstrated improved pharmacokinetics and targetability with minimum drug circulation in deep-seated organs upon delivery of DTX via pHS-LPHNPs in comparison with LPHNPs-DTX and free DTX. We observed sizeable % reduction in tumour-burden with pHS-LPHNPs-DTXthan that withLPHNPs-DTX &free DTX. In brief, pHS-LPHNPs mediated delivery of DTX exhibited promising approach for developing therapeutic-interventions against breast-cancer.

Synthesis, characterization and preliminary in vitro cellular uptake studies of 67Ga(III) thiosemicarbazones

2013 ◽  
Vol 33 ◽  
pp. 154-157 ◽  
Author(s):  
Tawfeeq Ismail ◽  
Daniel D. Rossouw ◽  
Philip Beukes ◽  
Jacobus P. Slabbert ◽  
Gregory S. Smith
Keyword(s):  
Cellular Uptake ◽  
Uptake Studies

scholarly journals In-vitro cytotoxicity and cellular uptake studies of luminescent functionalized core-shell nanospheres

2017 ◽  
Vol 24 (6) ◽  
pp. 1392-1403 ◽  
Author(s):  
Anees A. Ansari ◽  
T.N. Hasan ◽  
N.A. Syed ◽  
J.P. Labis ◽  
Ali A. Alshatwi
Keyword(s):  
Cellular Uptake ◽  
In Vitro Cytotoxicity ◽  
Core Shell ◽  
Uptake Studies

Impact of food components during in vitro digestion of silver nanoparticles on cellular uptake and cytotoxicity in intestinal cells

2015 ◽  
Vol 396 (11) ◽  
pp. 1255-1264 ◽  
Author(s):  
Dajana Lichtenstein ◽  
Johanna Ebmeyer ◽  
Patrick Knappe ◽  
Sabine Juling ◽  
Linda Böhmert ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cellular Uptake ◽  
In Vitro Digestion ◽  
Intestinal Cells ◽  
Digestion Process ◽  
X Ray Scattering ◽  
Food Components ◽  
Uptake Studies

Abstract Because of the rising application of nanoparticles in food and food-related products, we investigated the influence of the digestion process on the toxicity and cellular uptake of silver nanoparticles for intestinal cells. The main food components – carbohydrates, proteins and fatty acids – were implemented in an in vitro digestion process to simulate realistic conditions. Digested and undigested silver nanoparticle suspensions were used for uptake studies in the well-established Caco-2 model. Small-angle X-ray scattering was used to estimate particle core size, size distribution and stability in cell culture medium. Particles proved to be stable and showed radii from 3.6 to 16.0 nm. Undigested particles and particles digested in the presence of food components were comparably taken up by Caco-2 cells, whereas the uptake of particles digested without food components was decreased by 60%. Overall, these findings suggest that in vivo ingested poly (acrylic acid)-coated silver nanoparticles may reach the intestine in a nanoscaled form even if enclosed in a food matrix. While appropriate for studies on the uptake into intestinal cells, the Caco-2 model might be less suited for translocation studies. Moreover, we show that nanoparticle digestion protocols lacking food components may lead to misinterpretation of uptake studies and inconclusive results.

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