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Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of −52.2 to − 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher Cmax with the optimized formulation in comparison to pure drug suspension.

Irinotecan-loaded solid lipid nanoparticles (IRI-SLNs) was formulated and tested for its potential activity against colon cancer. IRI-SLNs were prepared by applying the principles of DoE. Nanoparticles were further surface modified using chitosan. Characterizations such as size, poly-dispersity, surface charge, morphology, entrapment, drug release pattern, cytotoxicity were conducted. In-vivo studies in male Wistar rats were carried to ascertain distribution pattern of SLNs and their acute toxicity on various vital organs. Lastly, stability of the SLNs were evaluated. Particles had a size, polydispersity and zeta potential of 430.77 ± 8.69 nm, 0.36 ± 0.02 and -40.06 ± 0.61 mV, respectively. Entrapment of IRI was 62.24 ± 2.90% in IRI-SLNs. Sustained drug release was achieved at a colonic pH and long-term stability of NPs was seen. Cytotoxicity assay results showed that SLNs exhibited toxicity on HCT-116 cells. Biodistribution studies confirmed higher concentration of drug in the colon after surface modification. An acute toxicity study conducted for 7 days showed no severe toxic effects on major organs. Thus, we picture that the developed SLNs may benefit in delivering IRI to the tumour cells, therefore decreasing the dose and dose-associated toxicities.