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Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for TNBC. First, the doxorubicin hydrochloride (Dox)-loaded genipin-crosslinked whey protein nanoparticles (WD) were prepared and optimised by the QbD method using BBD. The hydrodynamic diameter of WD was found to be 364.38 ± 49.23 nm, zeta potential -27.59 ± 1.038 mV, entrapment 63.03 ± 3.625% and Dox loading was found to be 1.419 ± 0.422%. The drug recovery after 18 months of storage was 69%. Then, it was incubated with NAC to obtain modified WD (CyWD). WD followed first-order release kinetics, whereas CyWD followed the Higuchi model. Hemagglutination and hemolysis were not found qualitatively in WD and CyWD. Upon injecting the nanoformulations to 4T1-induced mice, the highest efficacy was found to be in CyWD followed by WD and Dox injection. Upon histopathological observance, it was found that the CyWD group gave the most significant damage to the 4T1 tumour tissue. Thus, NAC-modified protein nanoparticles carrying chemotherapeutic agents can be an excellent targeted therapeutic system against TNBC.

There is a curious case in Alveolar macrophages (AM), the frontline defence recruits that contain the spread of all intruding bacteria. In response to Mycobacterium tuberculosis (M.tb), AM either contain the spread or are modulated by M.tb to create a region for their replication. The M.tb containing granulomas so formed are organised structures with confined boundaries. The limited availability of drugs inside AM aid drug tolerance and poor therapeutic outcomes in diseases like tuberculosis. The present work proves the glycotargeting efficiency of levofloxacin (LVF) to AM. The optimised formulation developed displayed good safety with 2% hemolysis and a viability of 61.14% on J774A.1 cells. The physicochemical characterisations such as Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) proved that carubinose linkage was accomplished and LVF is entrapped inside carubinose-linked hybrid formulation (CHF) and hybrid formulation (HF) in amorphous form. The transmission electron microscopy (TEM) images revealed a core-shell structure of HF. The particle size of 471.5 nm estimated through dynamic light scattering (DLS) is enough to achieve active and passive targeting to AM. The nanoparticle tracking analysis (NTA) data revealed that the diluted samples were free from aggregates. Fluorescence-activated cell sorting (FACS) data exhibited excellent uptake via CHF (15 times) and HF(3 times) with reference to plain fluorescein isothiocyanate (FITC). The pharmacokinetic studies revealed that CHF and HF release the entrapped moiety LVF in a controlled manner over 72 h. The stability studies indicated that the modified formulation remains stable over 6 months at 5 ± 3℃. Hence, hybrid systems can be efficiently modified via carubinose to target AM via the parenteral route.