pH Tunable Fluorescent Calcium Phosphate Nanocomposite for Sensing and Controlled Drug Delivery

Abstract

In this work, a novel pH sensitive calcium phosphate (CaP) nanocomposite capable of performing multiple tasks of controlled drug delivery, and simultaneous sensing by change in the fluorescence was fabricated. The nanocomposite was synthesized by encapsulating alendronate (AD) drug in CaP and modifying the surface with a fluorescent rhodamine B (RDB) dye. The multifunctional nanocomposite demonstrated high loading capacity for AD, excellent pH‐tunable AD release and optical sensing behavior, and good aqueous dispersity. Analysis by transmission electron microscopy and dynamic light scattering analysis revealed that RDB modified CaP/AD (RDB‐CaP/AD) nanocomposite had average dimensions of 21 nm × 44 nm and mean hydrodynamic size of 55 nm. The feasibility of CaP/AD nanocomposite for controlled drug delivery by pH responsive release was demonstrated by in vitro study at two different pH, 5.0 and 7.4. Furthermore, CaP/AD loaded with fluorescent RDB showed pH tunable fluorescence property, which can help in tracking the active state of the particle and give measurable indication of the drug delivery. In vitro study with osteoclast precursor cells, RAW 264.7 confirmed that CaP/AD nanocomposite significantly reduced the activity of osteoclast cells. The present study demonstrates that the fabricated multifunctional RDB‐CaP/AD nanocomposites can serve as an effective drug delivery vehicle capable of controlled drug release and sensing, simultaneously.

Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption

“…Tartrate resistant acid phosphatase (TRAP) activity, a characteristic of osteoclasts, was measured according to the protocol [23-25]. After 5, 8 and 14 days of culture, adherent osteoclast-like-cells were lysed in 1 M NaCl with 0.2% Triton x100.…”

Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review

“…Tissue/cell imaging is also possible by CaP NPs doped with lanthanum [86–89] or surface functionalized by organic dye molecules [75,76,90–92]. Lanthanum doping or surface functionalized dyes can act as fluorescing probes.…”

“…Simultaneous drug delivery and bio-imaging by a fluorescing probe was studied by Kester et al [75] and Banerjee et al [92]. Kester et al [75] encapsulated water-insoluble hydrophobic decanoyl ceramide (Cer 10 ), an anticancer drug, and rhodamine-WT (Rh-WT) dye into hydrophilic CaP NPs through double reverse-micelle approach.…”

“…Thus, CaP NPs could be very promising for targeted delivery of hydrophobic drugs like ceramide, which is not possible to administer through aqueous formulation [75]. In another study, a pH-sensitive release of Alendronate (AD) from CaP NPs is reported by Banerjee et al by synthesizing CaP-AD nanoconjugate [92]. AD is a bisphosphonate (BP) drug, which is used for bone diseases like osteoporosis.…”

Advanced bioactive and biodegradable ceramic biomaterials

“…In order to fully capitalise on their strong targeting potential and concomitant lower off-target effects in comparison with conventional drug agents, the entrapment of genetic material into calcium phosphate nanovehicles has been investigated (Giger et al , 2011). Stimulus responsive calcium phosphate nanocomposites have been investigated for concurrent sensing and drug delivery, where the release and fl uorescent response was triggered by changes in pH conditions (Banerjee et al , 2011). As such, these nanoparticles can be used for in vivo visualisation and treatment of cancerous tumours (Altinoglu et al , 2008;Kester et al , 2008;Morgan et al , 2008;Muddana et al , 2009).…”