Nanocarriers based oral lymphatic drug targeting: Strategic bioavailability enhancement approaches

Pandya, Priyanka; Giram, Prabhanjan S.; Bhole, Ritesh P.; Chang, Hsin‐I; Raut, Sushil

doi:10.1016/j.jddst.2021.102585

Cited by 17 publications

(11 citation statements)

References 122 publications

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“…Moreover, binding specific ligands on the surface of nanoparticles allow them to penetrate M cells through expressed receptors (Shreya et al 2019 ). For example, binding mannose ligands to nanoparticles increased loaded-drug delivery to LS through mannose receptors (Pandya et al 2021 ). Likewise, integrin was used as a binding ligand to enhance the LDD of orally administered therapeutic molecules through integrin receptors (Lin et al 2019 ).…”

Section: Type Lddmentioning

confidence: 99%

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

2023

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Lymphatic drug targeting is an effective approach for targeting immunomodulators, and chemotherapeutic drugs at a specific organ or cellular location. The cellular, paracellular, and dendritic cell trafficking machinery are involved in the lymphatic transport of therapeutic agents. The engineering of triggered and hybrid lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and microbial pandemics. Hybrid lymphatic drug delivery systems can be tailored and developed by grafting the conventional LDDS with biological agents. Thus, hybrid LDDS could collect the benefits of conventional and biological delivery systems. Moreover, the fabrication of triggered LDDS increases drug accumulation in the lymphatic system in the response to an internal stimulus such as pH, and redox status or external such as magnetic field, temperature, and light. Stimuli-responsive LDD systems prevent premature release of payload and mediate selective drug biodistribution. This improves therapeutic impact and reduces the systemic side effect of anticancer, immunomodulatory, and antimicrobial therapeutics. This review highlights the challenges and future horizons of nanoscaled-triggered LDDS and their influence on the lymphatic trafficking of therapeutic molecules. Graphical abstract

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Section: Type Lddmentioning

confidence: 99%

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

2023

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“…Intestinal lymphatic transport is considered an alternative drug delivery strategy. Targeting microfold cells (M cells) or forming chylomicrons (CMs) can mediate the entry of APIs into the systemic circulation through gut-associated lymphoid tissue [51]. For example, both Cholera toxin B subunit (CTB)-which is nontoxic to humans-and Ulex europaeus 1 (UEA-1) can specifically target M cells [52,53].…”

Section: Small Intestine-lymphatic Circulation Prevents the First-pas...mentioning

confidence: 99%

Recent Advances in Oral Peptide or Protein-Based Drug Liposomes

et al. 2022

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The high physiology and low toxicity of therapeutic peptides and proteins have made them a hot spot for drug development in recent years. However, their poor oral bioavailability and unstable metabolism make their clinical application difficult. The bilayer membrane of liposomes provides protection for the drug within the compartment, and their high biocompatibility makes the drug more easily absorbed by the body. However, phospholipids—which form the membranes—are subjected to various digestive enzymes and mucosal adhesion in the digestive tract and disintegrate before absorption. Improvements in the composition of liposomes or modifying their surface can enhance the stability of the liposomes in the gastrointestinal tract. This article reviews the basic strategies for liposome preparation and surface modification that promote the oral administration of therapeutic polypeptides.

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“…The proposed work comprises of combination approach to design stable, and targeted drug delivery system. Mannosylated chitosan is vital in lymphatic (M cell) targeting to enhance peptide oral delivery [20]. By attaching mannose molecules to chitosan, it gains the ability to interact with mannose receptors on specialized M cells in the intestinal mucosa [21].…”

Section: Introductionmentioning

confidence: 99%

Quality by design (QbD) approach-based development of optimized nanocarrier to achieve quality target product profile (QTPP)-targeted lymphatic delivery

Maurya,

Ramteke,

Jain

2024

Nanotechnology

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Background: Insulin, vital for diabetes management, faces challenges with poor permeability and stability, demanding enhanced effectiveness and safety measures. Various oral peptide delivery systems have emerged, but non-targeted ones, while preventing degradation, lack the ability to facilitate peptide transport. The limitation lies in their non-selectivity. Intestinal macrophage cells in gut-associated lymphoid tissue express carbohydrate-binding receptors (CBRs), ideal for receptor-mediated endocytosis and peptide delivery.Objective: This study aimed to create mannose ligand conjugated nanoparticles (MNPs) using a quality-by-design (QbD) approach to tackle oral administration challenges. The secondary objective was to identify factors influencing product quality. Lymphatic uptake of NPs was the quality target product profile (QTPP), and the study focused on critical formulation attributes (CFAs) like Mannosylated Chitosan concentrations (MCs) and TPP concentrations, as well as critical process parameters (CPP) such as stirring speed.Methods: MNPs, produced via inotropic gelation, were encapsulated in enteric-coated capsules for protection. The impact of CFAs and CPP on particle size and entrapment was observed through Box-Behnken design (BBD), statistically analyzed with ANOVA (p<0.05). Optimal conditions were determined using desirability values. Characterization involved HPLC, zeta-seizer analysis, SEM for morphology, MTT assay for safety, and cell-line studies for M-cell targeting.Results: SEM revealed oval-shaped NPs with an average size of 245.52±3.37 nm, surface potential of 22.12±2.13, and 76.15±1.3% drug entrapment. MTT assay affirmed safety, while confocal imaging indicated selective M-cell uptake.Conclusion: BBD facilitated optimized NP formulation, providing clear insights into variable significance. Cell-line studies confirmed safety and effective cellular uptake of the NPs.

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Nanocarriers based oral lymphatic drug targeting: Strategic bioavailability enhancement approaches

Cited by 17 publications

References 122 publications

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

Recent Advances in Oral Peptide or Protein-Based Drug Liposomes

Quality by design (QbD) approach-based development of optimized nanocarrier to achieve quality target product profile (QTPP)-targeted lymphatic delivery

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