Multifaceted therapeutic applications of biomimetic nanovaccines.

The development of vaccines has had a crucial role in preventing and controlling infectious diseases on a global scale. Innovative formulations of biomimetic vaccines inspired by natural defense mechanisms combine long-term antigen stability, immunogenicity, and targeted delivery with sustained release. Types of biomimetic nanoparticle (NP) include bacterial outer membrane vesicles (OMVs), cell membrane-decorated NPs, liposomes, and exosomes. These approaches have shown potential for cancer immunotherapy, and in antibacterial and antiviral applications. Despite current challenges, nanovaccines have immense potential to transform disease prevention and treatment, promising therapeutic approaches for the future. In this review, we highlight recent advances in biomimetic vaccine design, mechanisms of action, and clinical applications, emphasizing their role in personalized medicine, targeted drug delivery, and immunomodulation.

Polymeric Micelles for Breast Cancer Therapy: Recent Updates, Clinical Translation and Regulatory Considerations.

With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.

Therapeutic Potential of Naringenin Nanosuspension: In Vitro and In Vivo Anti-Osteoporotic Studies.

Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.

QbD aided development of ibrutinib-loaded nanostructured lipid carriers aimed for lymphatic targeting: evaluation using chylomicron flow blocking approach.

Ibrutinib (IBR) is the choice of drug for the treatment of chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL). IBR has low oral bioavailability of 2.9% owing to its high first pass metabolism. Present study was aimed to develop the nanostructured lipid carriers (NLC) using glyceryl monostearate (GMS) as solid lipid and Capryol™ PGMC as liquid lipid. Plackett-Burman design (PBD) was applied to screen the significant factors; furthermore, these significant factors were subjected to optimisation using Central Composite design (CCD). The size, poly dispersity index (PDI) and entrapment efficiency (E.E.) of the developed NLC were 106.4 ± 8.66 nm, 0.272 ± 0.005 and 70.54 ± 5.52% respectively. Morphological evaluation using transmission electron microscope (TEM) and field emission scanning electron microscope (FESEM) revealed spherical particles. Furthermore, differential scanning calorimetry (DSC) indicates the formation of molecular dispersion of drug in the melted lipid matrix while Powder X-Ray Diffraction (PXRD) studies reveal the absence of crystalline drug peaks in the formulation diffractogram. In-vivo pharmacokinetics of NLC displayed an increase in Cmax (2.89-fold), AUC0-t (5.32-fold) and mean residence time (MRT) (1.82-fold) compared with free drug. Furthermore, lymphatic uptake was evaluated by chylomicron flow blocking approach using cycloheximide (CXI). The pharmacokinetic parameters Cmax, AUC0-t and MRT of NLC without CXI were 2.75, 3.57 and 1.30 folds higher compared with NLC with CXI. The difference in PK parameters without CXI indicates significant lymphatic uptake of the formulation. Hence, NLC can be a promising approach to enhance the oral bioavailability of drugs with high first-pass metabolism. Graphical abstract.

Hansen solubility parameters for assay method optimization of simvastatin, ramipril, atenolol, hydrochlorothiazide and aspirin in human plasma using liquid chromatography with tandem mass spectrometry.

A simple, specific, sensitive, validated method was developed using liquid chromatography with tandem mass spectrometry with electrospray ionization of human plasma for the simultaneous estimation of drugs (simvastatin, ramipril, atenolol, hydrochlorothiazide, and aspirin) of PolycapTM capsule used in cardiovascular therapy. The interaction of these actives including internal standards between the stationary and mobile phase were investigated using Hansen solubility parameters. Chromatographic separation was performed on Phenomenex Synergi Polar-RP (30 × 2 mm, 4 µm) column with a gradient mobile phase composition of acetonitrile and 5 mM ammonium formate for positive mode and 0.1% formic acid in both water and acetonitrile for negative mode. The flow rate and runtime were 1.0 mL/min and 3.5 min, respectively. Sample extraction was done by protein precipitation using acetonitrile, enabling a fast analysis. The calibration ranges from 0.1 to 100, 0.1 to 100, and 1 to 1000 ng/mL for simvastatin, ramipril, and atenolol using internal standard carbamazepine in positive mode, respectively, whereas it was 0.3-300 and 2-2000 ng/mL for hydrochlorothiazide and aspirin using internal standard 7-hydroxy coumarin in negative mode, respectively. Hansen solubility parameters can be used as a high-throughput optimizing tool for column and mobile phase selection in bioanalysis. This validated bioanalytical method has the potential for future fixed dose combination based preclinical and clinical studies that can save analysis time.