Glycol chitosan stabilized nanomedicine of lapatinib and doxorubicin for the management of metastatic breast tumor

Kaur, Navneet; Mimansa,; Jaganathan, Mahendran; Munawara, Rafika; Aggarwal, Anjali; Shanavas, Asifkhan

doi:10.1007/s13346-023-01335-6

Cited by 10 publications

(2 citation statements)

References 62 publications

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“…In cancer cells, characterized by extreme complexity and interactions among dysregulated convergent and divergent cell signaling transduction pathways, the resistance mechanism of redundancy may represent the main cause of the failure or lack of efficacy Among approaches exploited to increase TKIs penetration of the BBB, nanoparticle (NPs) systems seem the most promising and performant; (a) NPs cross BBB easily and display enhanced permeability and retention in the tumor site; (b) NPs can be used as a shuttle system for many drugs and finally, (c) biodegradability of NPs limit their toxicity. In this context, a nanomedicine system co-loaded with lapatinib/doxorubicine and stabilized with glycol chitosan showed a potent therapeutic effect toward triple-negative breast cancer cells in comparison to a mixture of free drugs [22].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams

Serra,

Rubes,

Schinelli

et al. 2023

Cancers

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Metastasis is the main cause of anti-cancer therapy failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors, and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial-to-mesenchymal transition (EMT), thus promoting the colonization of distant sites that, in turn, sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules and biologics as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short review, we give an overview of the most recent advances related to important families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, KRAS inhibitors, and integrin antagonists. Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

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Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams

Serra,

Rubes,

Schinelli

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Administrations by solubility-enhancing techniques, long-acting injectable formulations, or lipid-based carrier systems are some of the possible approaches to overcoming the adverse biopharmaceutical properties of the drug. Several approaches such as polymeric micelles, amorphous solid dispersions, cyclodextrin complexes, nanofibers, albumin-bound nanoparticles, nanocrystals, nanosponges, , lipid hybrid nanoparticles, polymer-stabilized nanoparticles, and PEGylated liposomes have been attempted to enhance the pharmacokinetic and physicochemical properties of LTP and variously evaluated in vitro and in vivo . These works have attempted to improve the therapeutic effectiveness of LTP mostly by designing spatial-controlled release systems such as hyaluronic acid-coated LTP nanocrystals and surface functionalization to enhance blood circulation time.…”

Section: Introductionmentioning

confidence: 99%

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib

Singh,

Chakravarti,

Das

et al. 2024

Mol. Pharmaceutics

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Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pHdependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4-to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC 50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility−lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.

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Chitosan nanoparticles in tumor imaging and therapy

Zahed Nasab,

Akbari,

Mostafavi

et al. 2025

Fundamentals and Biomedical Applications of Chitosan Nanoparticles

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Glycol chitosan stabilized nanomedicine of lapatinib and doxorubicin for the management of metastatic breast tumor

Cited by 10 publications

References 62 publications

Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams

Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib

Chitosan nanoparticles in tumor imaging and therapy

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