Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

Abstract

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46±2%), while simultaneously preserving high viability (83±3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.

Molecular designing of nanoparticles and functional materials

“…37 Chemotherapeutic derivatives loaded on HAp/Ch-PLGA particles after in vitro studies showed a high potential as fine particle platform for a targeted and selective cancer therapy. 38 Solvent/non-solvent precipitation and freeze-drying were used for the synthesis and processing of HAp coated with Ch or Ch-PLGA nanoparticles with antimicrobial and osteoregenerative properties. 39 A thermogravimetric analysis coupled with on-line mass spectrometry confirmed the coating of the HAp with Ch or Ch-PLGA blend, while in vitro and in vivo studies justified the concept of blending Ch with PLGA in order to increase the quality of osteogenesis.…”

Multifunctional and hybrid systems based on calcium-phosphate and hydroxyapatite for preventive and regenerative medicine

“…Jedna od strategija dizajniranja materijala, na bazi nHAp-a je njihovo ojačavanje sintetskim polimernim matricama poput polil-laktida (PLLA) [56,57], poli(laktid-ko-glikolida), (PLGA) [58] ili prirodnim polimerima poput hitozana [59,60], kolagena [61], celuloze, elastina, keratina itd. [62].…”

“…Čestice na bazi nHAp/Ch/-PLGA su korišćene kao nosač jedinjenja A, (17β-hydroxy-17α-picolyl-androst-5-en-3β-yl acetate) hemoterapeutskog derivata androstana, koji pokazuje selektivnu antikancerogenu aktivnost prema ćelijama karcinoma pluća [60]. Kompozitni materijal A-HAp/Ch-PLGA bi potencijalno mogao da se koristi za selektivnu terapiju malignih ćelija pluća (slika 7).…”

“…Pokazano je da vitamin D, koji se koristi u tretmanu osteoporoze povoljno utiče na zarastanje preloma. TEHNIKA -NOVI MATERIJALI 26 (2017) 1 Slika 7 -Sinteza, karakterizacija i in vitro ispitivanja A-HAp/Ch-PLGA na ćelijama tumora pluća [60] Multifunkcionalni sistem na bazi nHAp-a [75] sintetizovan je kao direktni nosač holekalciferola (HAp/D3) u cilju njegove pulsne dostave, kao i nosač na bazi nHAp-a i PLGA u cilju kontrolisane dostave holekalciferola (HAp/D3/PLGA), slika 8.…”

Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles

“…They exhibit a good biocompatibility compared to other inorganic materials that biodegrade in biological fluids. With such fascinating properties, hydroxyapatite nanoparticles have shown many efforts in the delivery of drug and therapeutic agents with prolonged release [34][35][36][37][38][39]. Hydroxyapatite nanoparticles (HAPs) are of great interest in biomedical applications, such as bone regeneration [40,41].…”