Drug delivery to deep-seated tissues such as bone has been a major complication till date. This preferential drug delivery is further important in targeting anti-tumour agents to bone metastasis owing to its complexity. The present study involves the formulation of PLGA nanoparticles and conjugation with zolendronic acid-a bisphosphonate which will anchor the nanosystem to bone due to its selective bone affinity. The conjugated nanosystem was characterized for particle size by TEM (average 36 nm) and morphology by AFM depicting surface irregularities due to ZOL conjugation on the surface of nanoparticles. NMR spectral data also showed the involvement of terminal -OH group of PLGA in bond formation with ZOL. Bone localization studies showed higher accumulation of the ZOL-conjugated nanosystem in bone than non-conjugated nanoparticles. This was confirmed with bone mineral affinity and specificity assay wherein the conjugated nanosystem was found to selectively bind to hydroxyapatite in comparison to other bone minerals. The biodistribution studies depicted that the conjugated nanosystem was selectively targeted to the bone area with concentrations of methotrexate reaching up to 127.4 ± 1.41 μg in 1 h. Hence, this multipronged approach using (1) ultrasmall size of nanoparticles, (2) bone selective polymer and (3) suitable bone-targeting agent resulted in mutual synergism for the specific delivery of the anti-tumour agent to the bone.

Different nanoparticles, namely solid lipid nanoparticles, nanocrystals and nanosponges loaded with atorvastatin were successfully fabricated with desirable technological properties which reckoned promising methods of their preparation. Further, suitable characterization and evaluation parameters for in-vitro and in-vivo studies were conducted which led to increase in drug's bioavailability, provided better in-vivo efficacy and reduced toxicity in treating hyperlipidemia systemically. Particle sizes were found to be less than 300 nm with minimal polydispersity indices and maximized entrapment efficiency which are pre-requisites for their absorption in intestines. Drug release studies showed sustained release for a prolonged period, which was justified by release kinetics. Augmented bioavailability and reduced lipoprotein levels were key observations. In addition, reduced hepatotoxicty, decreased myotoxicity and diminished drug distribution were also the important highlights of these developed nanosystems as compared with the pure drug and marketed formulation. Histopathology of liver confirmed reduced hepatotoxicity. An elaborate comparison of these nanoparticles along with pure drug and marketed formulation concluded that nanosponges are potentially one of the best nanosystems for treating hyperlipidemia by systemic delivery.

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