Advances in Oral Drug Delivery

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 19, 2021

The oral route is the most common for drug administration. It preferred route, due to its advantages, such as non-invasiveness, patient compliance and convenience of Various factors govern absorption including solubility, mucosal permeability, stability in gastrointestinal tract environment. Attempts overcome these have focused on understanding physicochemical, biochemical, metabolic biological barriers which limit overall bioavailability. Different pharmaceutical technologies delivery systems nanocarriers, micelles, cyclodextrins lipid-based carriers been explored enhance absorption. To this end, review will discuss physiological, influencing bioavailability administration, well conventional novel strategies. challenges development aspects pediatric formulations also be addressed.

Language: Английский

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The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

Polymers, Journal Year: 2020, Volume and Issue: 12(2), P. 298 - 298

Published: Feb. 2, 2020

Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time improve drug efficacy. The conjugation of PEG proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) nanoparticles well-established technique known PEGylation, with PEGylated products have been using clinics for the last few decades. However, it increasingly recognized that treating patients drugs can lead formation antibodies specifically recognize bind (i.e., anti-PEG antibodies). Anti-PEG are also found who never treated but consumed containing PEG. Consequently, acquired results accelerated clearance, low efficacy, hypersensitivity, and, some cases, life-threatening side effects. In this succinct review, we collate recent literature draw attention polymer chemists issue immunogenicity delivery bioconjugation, thereby highlighting importance developing alternative polymers replace Several promising yet imperfect alternatives discussed. To achieve asatisfactory alternative, further joint efforts scientists related fields urgently needed design, synthesize evaluate new

Language: Английский

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Anti-PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 154-155, P. 163 - 175

Published: Jan. 1, 2020

Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method increase the therapeutic index complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering rise anti-drug antibodies (ADAs). Among ADAs, anti-PEG IgG IgM were shown account for efficacy loss due accelerated blood clearance (ABC phenomenon) hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition recapitulating basic information on PEG its applications, this review expands physicochemical factors influencing immunogenicity, prevalence, features, mechanism formation detection mechanisms by which (Abs) induce ABC HSRs. particular, we highlight in vitro, animal human data attesting Ab-induced complement (C) activation as common underlying cause both adverse effects. A main message that correct measurement Abs individual proneness C might predict immune PEGylated thereby their safety.

Language: Английский

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Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 659 - 659

Published: Feb. 19, 2023

Doxorubicin (DOX) constitutes the major constituent of anti-cancer treatment regimens currently in clinical use. However, precise mechanisms DOX’s action are not fully understood. Emerging evidence points to pleiotropic anticancer activity DOX, including its contribution DNA damage, reactive oxygen species (ROS) production, apoptosis, senescence, autophagy, ferroptosis, and pyroptosis induction, as well immunomodulatory role. This review aims collect information on DOX influence anti-tumor immune response, providing a rationale behind importance modern cancer therapy.

Language: Английский

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Nanomedicine in cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 7, 2023

Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances nanotechnology, accompanied by our growing understanding of biology and nano-bio interactions, have led development series nanocarriers, which aim improve efficacy while reducing off-target toxicity encapsulated anticancer agents through tumor tissue-, cell-, organelle-specific targeting. However, vast majority nanocarriers do not possess hierarchical targeting capability, their indices often compromised poor accumulation, inefficient cellular internalization, inaccurate subcellular localization. This Review outlines current prospective strategies design organelle-targeted nanomedicines, highlights latest progress technologies can dynamically integrate these three different stages static maximize outcomes. Finally, we briefly discuss challenges future opportunities for clinical translation nanomedicines.

Language: Английский

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RNAi-based therapeutics and tumor targeted delivery in cancer

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 182, P. 114113 - 114113

Published: Jan. 19, 2022

Language: Английский

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Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

Molecules, Journal Year: 2020, Volume and Issue: 25(11), P. 2692 - 2692

Published: June 10, 2020

RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers achieve efficient delivery of siRNAs into vivo, including tumor and/or host the micro-environment (TME). Consequently, lipid polymer-based nanoparticle siRNA systems have been developed surmount these barriers. In this article, we review strategies that facilitate survival circulatory system, movement from blood tissues TME, targeted or specific cell types, cellular uptake, escape endosomal degradation. We also discuss use various types carriers therapy, a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, current recent clinical trials using NPs loaded with The therapeutics field is rapidly evolving, it conceivable precision therapy could, relatively near future, benefit combined therapies, example immune checkpoint blockade together gene-targeting siRNAs, personalized enhancing fine-tuning patient’s therapeutic response.

Language: Английский

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Biomimetic cell membrane‐coated poly(lactic‐ co ‐glycolic acid) nanoparticles for biomedical applications

Bioengineering & Translational Medicine, Journal Year: 2022, Volume and Issue: 8(2)

Published: Nov. 2, 2022

Abstract Poly(lactic‐ co ‐glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability sustained controlled release. To prolong NP circulation time, enable target‐specific overcome physiological barriers, NPs camouflaged in cell membranes have been developed evaluated to improve delivery. Here, we discuss recent advances membrane‐coated PLGA NPs, preparation methods, application cancer therapy, management inflammation, treatment cardiovascular disease control infection. We address the current challenges highlight future research directions needed effective use membrane‐camouflaged NPs.

Language: Английский

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Recent Progress of Lipid Nanoparticles-Based Lipophilic Drug Delivery: Focus on Surface Modifications

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 772 - 772

Published: Feb. 26, 2023

Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic used for treating diseases through delivery routes, including skin absorption, oral administration, injection. However, a low solubility in the body, drug systems (DDSs) being actively developed increase bioavailability. Liposomes, micro-sponges, polymer-based nanoparticles been proposed DDS carriers drugs. their instability, cytotoxicity, lack targeting ability limit commercialization. Lipid (LNPs) fewer side effects, excellent biocompatibility, high physical stability. LNPs considered efficient vehicles owing lipid-based internal structure. In addition, recent LNP studies suggest that bioavailability can be increased surface modifications, PEGylation, chitosan, surfactant protein coating. Thus, combinations an abundant utilization potential fields DDSs carrying this review, functions efficiencies types modifications optimize discussed.

Language: Английский

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Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 357, P. 161 - 174

Published: March 30, 2023

The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field neuro-oncology. presence blood barrier (BBB) along with highly invasive and aggressive nature presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is first line agent used clinic it has been useful increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, short plasma half-life (2 h), subjected P-gp efflux, limited extravasation (∼20%). It postulated that reducing efflux tissue exposure could prove treating preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have loaded TMZ, surface PEGlyated reduce decorated cascade targeting protein lactoferrin efficient uptake across BBB into glioblastoma. Our results demonstrate USLP improves permeability vitro evidenced using transwell model which mimics endothelial tight junctions permeation being enhanced PEGylated particles. Data also suggests formulations can significantly ratio TMZ. In apoptosis studies on cell lines U87 GL261 were conducted showed an improvement induced compared pure Finally, proof-of-concept preclinical mouse study demonstrated when given intravenously at 50 mg/kg, particles accumulation within few hours without any obvious pathophysiological changes vital organs assessed via histology. Overall, data our innovative delivery system permeating potential improve efficacy therapy.

Language: Английский

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