Search

The present research work was designed to develop dorzolamide-loaded chitosan-coated polycaprolactone nanoparticles (DRZ-CS-PCL-NPs) for improved ocular delivery. The nanoparticles were prepared by single-step emulsification technique and optimized using the three-factor three-level Box-Behnken design. The optimized DRZ-CS-PCL-NPs prepared with the composition of polycaprolactone (60 mg), chitosan (0.6%) and polyvinyl alcohol (1.5%). The particle size, polydispersity index, zeta potential and encapsulation efficiency of optimized DRZ-CS-PCL-NPs were found to be 192.38 ± 6.42 nm, 0.18 ± 0.04, +5.21 ± 1.24 mV, and 72.48 ± 5.62%, respectively. The dependent and independent response variables showed excellent correlation and signifying the rationality of the optimized DRZ-CS-PCL-NPs. The DRZ release from CS-PCL-NPs showed biphasic behaviour with initial burst release for 2 h after that sustained-release up to 12 h of study. The corneal flux experiment showed many fold enhancement in permeation across goat cornea. DRZ-CS-PCL-NPs exhibited 3.7 fold higher mucoadhesive strength compared to the control. Furthermore, the histopathological assessment and HET-CAM study revealed that the DRZ-CS-PCL-NPs were non-irritant and safe for ocular administration. Therefore, from the present study, it can be concluded that the optimized DRZ-CS-PCL-NPs are safe and have the potential for successful ocular delivery and improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Cancer development is associated with abnormal, uncontrolled cell growth and causes significant economic and social burdens to society. The global statistics of different cancers have been increasing because of the aging population, and the increasing prevalence of risk factors such as stress condition, overweight, changing reproductive patterns, and smoking. The prognosis of cancer treatment is high, if diagnosed in the early stage. Late-stage diagnosis, however, is still a big challenge for the clinician. The usual treatment scheme involves chemotherapy and surgery followed by radiotherapy. Chemotherapy is the most widely used therapeutic approach against cancer. However, it suffers from the major limitation of poor delivery of anticancer therapeutics to specific cancer-targeted tissues/cells. Nanomedicines, particularly nanostructured lipid carriers (NLCs) can improve the efficacy of encapsulated payload either through an active or passive targeting approach against different cancers. The targeted nanomedicine can be helpful in transporting drug carriers to the specifically tumor-targeted tissue/cells while sparing abstaining from the healthy tissue/cells. The active targeting utilizes the binding of a specific cancer ligand to the surface of the NLCs, which improves the therapeutic efficacy and safety of the cancer therapeutics. This review shed light on the utilization of NLCs system for targeted therapy in different cancers. Furthermore, modification of NLCs as cancer theranostics is a recent advancement that is also discussed in the manuscript with a review of contemporary research carried out in this field. [Display omitted] • NLCs as second generation lipid nanocarrier gained attention for cancer treatment. • It can be exploited to deliver wide variety of cancer therapeutics. • The efficacy of encapsulated therapeutic improved significantly in cancer by NLCs. • Recent advancement leads its applicability as cancer theranostics. • Biocompatible lipids nature of NLCs makes them candidates of clinical significance. [ABSTRACT FROM AUTHOR]

• TNBC represents the most aggressive phenotype of breast cancer. • Conventional therapy prescribed for breast cancer is not effective in treatment of TNBC. • Specific therapeutic targets must be identified in TNBC. • The PI3K/Akt/Mtor (PAM) pathway is an important signaling pathway of TNBC. • Drug molecules targeting the PAM pathway could emerge as promising therapeutics. Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer associated with poor prognosis. Although conventional chemotherapy regimens have shown some effectiveness in early TNBC cases, the outcome in advanced stages is poor. The PI3K/AKT/mTOR pathway is one of the important and active pathways involved in chemoresistance and survival of TNBC. This pathway is speculated to play an important part in malignant transformation and has been considered as a potential molecular target for the design of therapeutic agents to treat TNBC. This review discusses the potentials and drug discovery perspectives of PI3K/AKT/mTOR as a therapeutic target for effective management of TNBC with anticipated challenges. [ABSTRACT FROM AUTHOR]