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1.
J Colloid Interface Sci ; 591: 440-450, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33631531

ABSTRACT

Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.


Subject(s)
Breast Neoplasms , Chitosan , Nanoparticles , Breast Neoplasms/drug therapy , Cell Line, Tumor , Drug Carriers/therapeutic use , Drug Liberation , Female , Humans , Microfluidics
2.
Curr Top Med Chem ; 18(14): 1224-1241, 2018.
Article in English | MEDLINE | ID: mdl-30095053

ABSTRACT

The use of colloidal particles as drug delivery carriers holds a great promise in terms of improvement of traditional treatment and diagnosis of human diseases. Nano- and microsized particles of a different composition including organic and inorganic materials can be fabricated with a great control over size, shape and surface properties. Nevertheless, only some few formulations have surpassed the benchtop and reached the bedside. The principal obstacle of colloidal drug delivery systems is their poor accumulation in target tissues, organs and cells, mainly by efficient sequestration and elimination by the mononuclear phagocytic system. Recent evidence suggests that, besides size, the surface character of colloidal systems is the most determinant design parameter that may ultimately guarantee successful biological performance. To approach these issues, materials designers and engineers can make use of multiple strategies and tools to finely modulate the particles' surface towards highly efficient and biocompatible materials. In this article, we provide an overview of the most relevant colloidal drug delivery systems, a summary of the available literature regarding the effects of surface charge, hydrophobicity and softness on biological response, and finally, we review the key points of surface modification strategies with organic, inorganic and biological materials.


Subject(s)
Colloids/chemistry , Drug Delivery Systems , Pharmaceutical Preparations/chemistry , Animals , Electrochemistry , Humans
3.
J Colloid Interface Sci ; 518: 122-129, 2018 May 15.
Article in English | MEDLINE | ID: mdl-29453102

ABSTRACT

The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.


Subject(s)
Antineoplastic Agents/chemistry , Breast Neoplasms/drug therapy , Drug Carriers/chemistry , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Rose Bengal/chemistry , Adsorption , Antineoplastic Agents/therapeutic use , Biological Transport , Cell Line, Tumor , Cell Survival/drug effects , Colloids , Drug Carriers/therapeutic use , Drug Liberation , Emulsions , Humans , Lactic Acid/chemical synthesis , Optical Imaging , Particle Size , Polyglycolic Acid/chemical synthesis , Polylactic Acid-Polyglycolic Acid Copolymer , Static Electricity , Surface Properties
4.
J Agric Food Chem ; 65(43): 9435-9442, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28942644

ABSTRACT

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1% inhibition of inflammatory pain at 2.5 mg/kg ip and 50.0 ± 15.9% inhibition of edema formation at 5 mg/kg ip) and acute analgesia (66.1 ± 28.1% inhibition at 5.0 mg/kg ip) were observed. Moreover, guineensine inhibited proinflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy, but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant, but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels, and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A, and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.


Subject(s)
Alkenes/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Edema/drug therapy , Endocannabinoids/metabolism , Heterocyclic Compounds, 2-Ring/administration & dosage , Inflammation/drug therapy , Piper nigrum/chemistry , Plant Extracts/administration & dosage , Animals , Edema/metabolism , Endocannabinoids/antagonists & inhibitors , Humans , Inflammation/metabolism , Male , Mice , Mice, Inbred BALB C , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Seeds/chemistry
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