Abstract
We engineered nanomedicine with the stealth corona made up of densely packed bone seeking ligand, alendronic acid. In a typical nanoconstruct, alendronic acid is conjugated with hydrophilic head moiety of phospholipid that has an ability to self-assemble with hydrophobic polymeric core through its hydrophobic long carbon-chain. Proposed nanomedicine has three distinct compartments namely; poly(l-lactic-co-glycolic acid) polymeric core acting as a drug reservoir and skeleton of the nanoconstruct, phospholipid monolayer covers the core acting as a diffusion barrier, and a densely packed alendronic acid corona acting as a stabilizer and targeting moiety. Thus engineered nanomedicine attain spherical entity with ~90 ± 6 nm having negative zeta potential, −37.7 ± 2 mV, and has an ability to load 7 ± 0.3 wt% of doxorubicin. In-vitro bone targeting efficiency of nanomedicine was studied using hydroxyapatite crystals as a bone model, and found significant accumulation of nanoparticle in the crystals. Moreover, cellular internalization studies with mouse osteosarcoma confirm the selectivity of nanomedicine when compared to its internalization in non-targeted mouse melanoma. This nanomedicine shows prolong stability in serum and deliver the drug into the cell exhibiting an IC50 of 3.7 μM. Given the strong interacting property of alendronic acid with bone, the proposed nanomedicine hold promises in delivering drug to bone microenvironment.
Highlights
According to the American Cancer Society, an estimated 3,300 new cases of primary bone cancer are expected to occur during 20161
In a recent study conducted by Swami et al, bortezomid, a proteasome inhibitor, loaded polymeric nanoparticle was proposed, in which the stealth polyethylene glycol (PEG) corona was conjugated with alendronic acid to target bone[17]
Considering the important role of hydrophilic corona layer on the surface of nanoconstruct in stabilizing nanosystem, we hypothesized that the Alendronic acid moiety with hydrophilic phosphate groups could provide favorable environment for water to form hydration layer around the particle protecting it from opsonization when properly structured in nanoconstruct and further sustain the stability of nanosystem under physiological condition
Summary
According to the American Cancer Society, an estimated 3,300 new cases of primary bone cancer are expected to occur during 20161. Considering the important role of hydrophilic corona layer on the surface of nanoconstruct in stabilizing nanosystem, we hypothesized that the Alendronic acid moiety with hydrophilic phosphate groups could provide favorable environment for water to form hydration layer around the particle protecting it from opsonization when properly structured in nanoconstruct and further sustain the stability of nanosystem under physiological condition To this end, we proposed a targeted nanoparticle (TNP) which is made up of Alendronic acid modified lipid and PLGA polymeric core encapsulating chemotherapeutic drug - Doxorubicin (DOX) to simultaneously offer combinatorial actions including targeting and therapy of bone cancer treatment. The engineered nanomedicine has stealth properties providing by bone mineral targeting moiety and deliver a large quantitative amount of therapeutic agent which could enhance the effectiveness of treatment
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