Synergistic anticancer efficacy of Bendamustine Hydrochloride loaded bioactive Hydroxyapatite nanoparticles: In-vitro, ex-vivo and in-vivo evaluation

Thomas, Shindu C.; Sharma, Harshita; Rawat, Purnima; Verma, Anita; Leekha, Ankita; Kumar, Vijay; Tyagi, A. K.; Gurjar, Bahadur Singh; Iqbal, Zeenat; Talegaonkar, Sushama

doi:10.1016/j.colsurfb.2016.07.035

Cited by 18 publications

(7 citation statements)

References 36 publications

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“…The development of controlled drug delivery systems has become essential to reduce drug concentrations and provide long-term therapeutic effects [16][17][18][19]. HAp has been applied substantially as a carrier for the controlled delivery of different types of therapeutic agent (e.g., drugs, genes, antigens, enzymes, proteins) [20,21]. Basic factors in drug release, such as pore size, surface area and surface functionalization can be easily controlled in HAp systems [22].…”

Section: Introductionmentioning

confidence: 99%

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

Kadkhodaie-Elyaderani

Lama-Odría

Rivas

et al. 2022

IJMS

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The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.

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Section: Introductionmentioning

confidence: 99%

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

Kadkhodaie-Elyaderani

Lama-Odría

Rivas

et al. 2022

IJMS

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“…HAp particles have great received interest as carriers for drug delivery systems due to the facility to control texture, porosity, surface area, and even to allow their surface functionalization. In fact, HAp has been employed for the release of a large variety of therapeutic agents [19,20,21]. Thus, ACP and cHAp are calcium phosphates that differ in their crystallinity and have similar composition and Ca/P ratio.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of Chloramphenicol Loaded Hydroxyapatite Nanoparticles into Polylactide

Rivas

Pelechà

Franco

et al. 2019

IJMS

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Chloramphenicol (CAM) has been encapsulated into hydroxyapatite nanoparticles displaying different morphologies and crystallinities. The process was based on typical precipitation of solutions containing phosphate and calcium ions and the addition of CAM once the hydroxyapatite nuclei were formed. This procedure favored a disposition of the drug into the bulk parts of the nanoparticles and led to a fast release in aqueous media. Clear antibacterial activity was derived, being slightly higher for the amorphous samples due to their higher encapsulation efficiency. Polylactide (PLA) microfibers incorporating CAM encapsulated in hydroxyapatite nanoparticles were prepared by the electrospinning technique and under optimized conditions. Drug release experiments demonstrated that only a small percentage of the loaded CAM could be delivered to an aqueous PBS medium. This amount was enough to render an immediate bacteriostatic effect without causing a cytotoxic effect on osteoblast-like, fibroblasts, and epithelial cells. Therefore, the prepared scaffolds were able to retain CAM-loaded nanoparticles, being a reservoir that should allow a prolonged release depending on the polymer degradation rate. The studied system may have promising applications for the treatment of cancer since CAM has been proposed as a new antitumor drug.

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“…Volume and weight of all the animals was taken after every fifth day; volume was measured using vernier calipers. Tumor volume and weight of each group were taken until 30 days and evaluated in each case …”

Section: Methodsmentioning

confidence: 99%

Bendamustine–PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo Pharmacokinetics: A Sustainable Delivery Tactic

et al. 2017

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Successful delivery of a chemotherapeutic agent like bendamustine still remains a challenge in clinical conditions like chronic lymphatic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma. We have conjugated bendamustine to polyamidoamine (PAMAM) dendrimers after conjugating with N-(hydroxyethyl)maleimide (spacer) via an ester bond. The particle size of PAMAM-bendamustine conjugate was 49.8 ± 2.5 nm. In vitro drug release resulted in sustained release with improved solution stability of drug up to 72 h. In a 24 h cytotoxicity study by MTT assay against human monoblastic leukemia cells (THP-1), the IC50 value for PAMAM-bendamustine was 32.1 ± 4.8 μM compared to 50.42 ± 3.4 μM and 2303 ± 106.5 μM for bendamustine and PAMAM dendrimer, respectively. Significantly higher cell uptake and apoptosis were observed in THP-1 cells by PAMAM-bendamustine conjugate which was confirmed by flow cytometry and confocal laser scanning microscopy. Preliminary in vivo studies undertaken included pharmacokinetics studies, organ distribution studies, and tumor inhibition studies. In healthy Wistar rat model (1CBM IV push model), the pharmacokinetic studies revealed that bioavailability and t increased significantly, i.e., almost 8.5-fold (193.8 ± 1.116 vs 22.8 ± 0.158 μg mL/h) and 5.1-fold (0.75 ± 0.005 vs 3.85 ± 0.015 h), respectively, for PAMAM-bendamustine conjugate compared to pure bendamustine ( p < 0.05), however, clearance and volume of distribution were found to be decreased compared to those of free drug. The study suggests that PAMAM-bendamustine conjugate was not only stable for the longer period but also least toxic and highly taken up by THP-1 cells to exert an anticancer effect at the reduced dose. Tumor inhibition and biodistribution studies in tumor-bearing BALB/c mice revealed that PAMAM-bendamustine conjugate was more effective than the pure drug and showed higher accumulation in the tumor.

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Synergistic anticancer efficacy of Bendamustine Hydrochloride loaded bioactive Hydroxyapatite nanoparticles: In-vitro, ex-vivo and in-vivo evaluation

Cited by 18 publications

References 36 publications

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

Incorporation of Chloramphenicol Loaded Hydroxyapatite Nanoparticles into Polylactide

Bendamustine–PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo Pharmacokinetics: A Sustainable Delivery Tactic

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