Intracellular Delivery Of Hydrophobic Drugs Research Articles

Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles’ Physicochemical Properties on Responses in Biological Systems

In the last four decades, nanotechnology has gained momentum with no sign of slowing down. The application of inventions or products from nanotechnology has revolutionised all aspects of everyday life ranging from medical applications to its impact on the food industry. Nanoparticles have made it possible to significantly extend the shelf lives of food product, improve intracellular delivery of hydrophobic drugs and improve the efficacy of specific therapeutics such as anticancer agents. As a consequence, nanotechnology has not only impacted the global standard of living but has also impacted the global economy. In this review, the characteristics of nanoparticles that confers them with suitable and potentially toxic biological effects, as well as their applications in different biological fields and nanoparticle-based drugs and delivery systems in biomedicine including nano-based drugs currently approved by the U.S. Food and Drug Administration (FDA) are discussed. The possible consequence of continuous exposure to nanoparticles due to the increased use of nanotechnology and possible solution is also highlighted.

Exploring Poly(Ethylene Glycol)-Poly(Trimethylene Carbonate) Nanoparticles as Carriers of Hydrophobic Drugs to Modulate Osteoblastic Activity

Current treatment options for bone-related disorders rely on a systemic administration of therapeutic agents that possess low solubility and intracellular bioavailability, as well as a high pharmacokinetic variability, which in turn lead to major off-target side effects. Hence, there is an unmet need of developing drug delivery systems that can improve the clinical efficacy of such therapeutic agents. Nanoparticle delivery systems might serve as promising carriers of hydrophobic molecules. Here, we propose 2 nanoparticle-based delivery systems based on monomethoxy poly(ethylene glycol)-poly(trimethyl carbonate) (mPEG-PTMC) and poly(lactide-co-glycolide) for the intracellular controlled release of a small hydrophobic drug (dexamethasone) to osteoblast cells in vitro. mPEG-PTMC self-assembles into stable nanoparticles in the absence of surfactant and shows a greater entrapment capacity of dexamethasone, while assuring bioactivity in MC3T3-E1 and bone marrow stromal cells cultured under apoptotic and osteogenic conditions, respectively. The mPEG-PTMC nanoparticles represent a potential vector for the intracellular delivery of hydrophobic drugs in the framework of bone-related diseases.

Dual Stimuli-Responsive Hybrid Polymeric Nanoparticles Self-Assembled from POSS-Based Starlike Copolymer-Drug Conjugates for Efficient Intracellular Delivery of Hydrophobic Drugs.

To further fine tune drug release and enhance therapeutic effects of polyhedral oligomericsilsesquioxane (POSS)-based nanomedicine, a starlike organic-inorganic conjugate was synthesized by grafting semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers to a POSS rigid core through reductively degradable disulfide bonds. The hydrophobic docetaxel (DTX) was attached to the grafts by pH-sensitive hydrazone bonds and also encapsulated into the POSS core (SP-DTX). Thus, the final amphiphilic star-shaped conjugates could self-assemble into nanoparticles and exhibited conspicuous drug-loading capacity (20.1 wt %) based on the covalently conjugated accompanied by physically encapsulated DTX. The stimuli-responsive DTX release under acidic lysosomal and reducing cytoplasmic environments was verified, leading to enhanced cytotoxicity against PC-3 human prostate carcinoma cells. To evaluate the in vivo therapeutic effects of the DTX-loaded nanovehicles objectively, a stroma-rich, prostate xenograft tumor model was generated. SP-DTX displayed uniform tumor distribution and suppressed tumor growth to a more pronounced level (tumor inhibition of 78.9%) than nonredox-sensitive SP-DTX-A (67.4%), SP-DTX-C contained DTX only in the core (65.5%) or linear P-DTX (60.7%) through enhanced depletion of cancer-associated fibroblasts and induction of apoptosis. The hybrid POSS-based polymeric nanoparticles offer an efficient approach to transport hydrophobic drugs for cancer therapy.

POEGMA-based disulfide-containing fluorescent probes for imitating and tracing noninternalization-based intracellular drug delivery.

POEGMA-based disulfide-containing fluorescent probes were designed and synthesized to enable the real-time and quantitative analysis of the (bio)reduction of disulfides within the polymeric backbones in complex redox media and in the presence of cells. This study lights up the way of exploiting bioreduction in the extracellular spaces for the delivery of hydrophobic drugs.

Erratum to: Contact-mediated intracellular delivery of hydrophobic drugs from polymeric nanoparticles

© 2015 Snipstad et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. ERRATUM Snipstad et al. Cancer Nano (2015) 6:3 DOI 10.1186/s12645‐015‐0011‐4

Contact-mediated intracellular delivery of hydrophobic drugs from polymeric nanoparticles.

Encapsulation of drugs in nanoparticles can enhance the accumulation of drugs in tumours, reduce toxicity toward healthy tissue, and improve pharmacokinetics compared to administration of free drug. To achieve efficient delivery and release of drugs at the target site, mechanisms of interaction between the nanoparticles and cells and the mechanism of delivery of the encapsulated drug are crucial to understand. Our aim was to determine the mechanisms for cellular uptake of a fluorescent hydrophobic model drug from poly(butylcyanoacrylate) nanoparticles. Prostate adenocarcinoma cells were incubated with Nile Red-loaded nanoparticles or free Nile Red. Uptake and intracellular distribution were evaluated by flow cytometry and confocal laser scanning microscopy. The nanoparticles mediated a higher intracellular level and more rapid uptake of encapsulated Nile Red compared to model drug administered alone. The main mechanism for delivery was not by endocytosis of nanoparticles but by nanoparticle-cell contact-mediated transfer directly to the cytosol and, to a smaller extent, release of payload from nanoparticles into the medium followed by diffusion into cells. The payload thus avoids entering the endocytic pathway, evading lysosomal degradation and instead gains direct access to intracellular targets. The nanoparticles are promising tools for efficient intracellular delivery of hydrophobic anticancer drugs; therefore, they are clinically relevant for improved cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12645-014-0008-4) contains supplementary material, which is available to authorized users.

PH-Responsive wormlike micelles for intracellular delivery of hydrophobic drugs

pH-Responsive wormlike micelles for intracellular delivery of hydrophobic drugs

Intracellular pH-activated PEG-b-PDPA wormlike micelles for hydrophobic drug delivery

Wormlike micelles with intracellular pH-activating properties were developed. The micelles remained in a “silent” state at physiological pH conditions (i.e. pH 7.4), but were activated in the acidic microenvironment of endocytic vesicles. The wormlike micelles could be employed as nanovectors for the intracellular delivery of hydrophobic drugs for cancer therapy.

Amphiphilic Homopolymer Vesicles as Unique Nano-Carriers for Cancer Therapy

A unique polymersome from amphiphilic, norbornene-derived thiobarbiturate homopolymers (NDTH) and its application as nanocarrier for cancer therapy are elaborately discussed. Various experiments like structural characterizations, control studies, cell viability studies, encapsu- lation studies, and MTT assay against 4T cancer cells are performed on these NDTH polymersomes to substantiate our claims. All of these results demonstrate that these self-assembled NDTH vesicles have great scope in the world of medicine, and they also symbolize promising carriers for the stimuli-triggered intracellular delivery of hydrophobic drugs.

Reversible pH- and Lipid-Sensitive Vesicles from Amphiphilic Norbornene-Derived Thiobarbiturate Homopolymers.

Synthesis of a new molecular architecture, an amphiphilic, norbornene-derived thiobarbiturate homopolymer (NTBH), by ring-opening metathesis polymerization (ROMP) and its characterization is discussed. The newly designed hompolymer shows a self-assembled vesicle formation in aqueous solution. Dynamic light scattering and critical aggregation concentration studies confirm the aggregate formation in solution while atomic force microscopy and transmission electron microscopy of the dried sample on the silicon substrate further confirm the vesicular morphologies of these amphiphilic homopolymers. Encapsulation studies of hydrophilic doxorubicin and hydrophobic Nile red suggest the reversible nature of the NTBH vesicles. Dye release studies in acidic and lipophilic environment demonstrate the stimuli-responsive nature of the novel systems. The results demonstrate that these self-assembled NTBH vesicles have great scope in the field of medicine as they symbolize themselves as promising carriers for the stimuli-triggered intracellular delivery of hydrophobic drugs.

A double-targeted magnetic nanocarrier with potential application in hydrophobic drug delivery

A double-targeted magnetic nanocarrier based with potential applications in the delivery of hydrophobic drugs has been developed. It consists of magnetite (Fe 3O 4) nanoparticles encapsulated in self-assembled micelles of the amphiphilic copolymer MPEG–PLGA [methoxy poly (ethylene glycol)-poly ( d, l-lactide-co-glycolide)], and was fabricated using the solvent-evaporation technique. The magnetic nanocarrier has a very stable core–shell structure and is superparamagnetic. Its cytotoxicity was evaluated using the MTT assay with three cell lines—HeLa, MCF-7, and HT1080; it exhibited no cytotoxicity against any tested line at concentrations of up to 400 μg/mL after incubation for 24 h. Its cellular uptake was studied by Prussian blue staining and by fluorescence microscopy after encapsulating a fluorescent probe (hydrophobic quantum dots) into the nanocarrier. Finally, the magnetic targeting property of the magnetic nanocarrier was confirmed by an in vitro test. Overall, the results obtained demonstrate the potential of the double-targeted nanocarrier for the intracellular delivery of hydrophobic drugs.

ABC block copolymer as “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs

Amphiphilic triblock copolymer of poly(ethylene glycol)-block-poly(dimethylaminoethyl methacrylate)-block-poly(ε-caprolatone) (PEG-PDMA-PCL) was synthesized using a one-pot sequential oxyanionic polymerization of DMA and ε-CL, associated with a PEG-O −K + macroinitiator. The pH-responsive micellization behavior of the copolymer was studied using dynamic light scattering (DLS), steady–state fluorescence and TEM techniques. The anti-cancer drug of doxorubicin (DOX) was chosen as a model drug to investigate the potential application of this triblock copolymer in drug controlled release. The results indicated the important roles of the PCL block for drug loading, the PDMA block for pH-responsive release, and PEG block for good bio-affinity. Cell cytotoxicity tests showed that the DOX-loaded PEG-PDMA-PCL micelles were pharmaceutically active to suppress the growth of SKOV-3 cells. This novel stimuli–responsive block copolymer is an attractive candidate as the “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs.

Cucurbituril-based nanoparticles: a new efficient vehicle for targeted intracellular delivery of hydrophobic drugs

Cucurbituril-based nanoparticles (CB[6]NPs) serve as new efficient vehicles for delivery of hydrophobic drugs, which have unique features including (1) a high drug loading capacity and efficiency, (2) noncovalently tunable surfaces, (3) efficient delivery of hydrophobic drugs into a cancer cell by receptor-mediated endocytosis, and (4) facile release of drugs into cytoplasm, which enhances the pharmaceutical effects of the drugs.