Quality by design endorsed atorvastatin-loaded nanostructured lipid carriers embedded in pH-responsive gel for melanoma.

AIM: Our aim was to repurpose atorvastatin for melanoma by encapsulating in a nanostructured lipid carrier matrix to promote tumour cell internalisation and skin permeation. pH-responsive chitosan gel was employed to restrict At-NLCs in upper dermal layers. METHODS: We utilised a quality by design approach for encapsulating At within the NLC matrix. Further, cellular uptake and cytotoxicity was evaluated along with pH-responsive release and ex vivo skin permeation. RESULTS: Cytotoxicity assay showed 3.13-fold enhanced cytotoxicity on melanoma cells compared to plain drug with nuclear staining showing apoptotic markers. In vitro, release studies showed 5.9-fold rapid release in chitosan gel matrix at pH 5.5 compared to neutral pH. CONCLUSIONS: At-NLCs prevented precipitation, promoted skin permeation, and SK-MEL 28 cell internalisation. The localisation of NLCs on the upper dermal layer due to electrostatic interactions of skin with chitosan gel diminished the incidence of untoward systemic effects.

Quality by design steered development of Niclosamide loaded liposomal thermogel for Melanoma: In vitro and Ex vivo evaluation.

Melanoma is the most malignant form of skin cancer across the globe. Conventional therapies are currently ineffective which could be attributed to the rampant chemo-resistance, metastasis, inability to cross the skin barriers and accumulate within the tumor microenvironment. This advent brings in the principles of drug repurposing by repositioning Niclosamide (NIC), an anthelmintic drug for skin cancer. Incorporation into the liposomes facilitated enhanced melanoma cell uptake and apoptosis. Cytotoxicity studies revealed 1.756-fold enhancement in SK-MEL-28 cytotoxicity by NIC-loaded liposomes compared to free drug. Qualitative and quantitative cell internalization indicated greater drug uptake within the melanoma cells illustrating the efficacy of liposomes as efficient carrier systems. Nuclear staining showed blebbing and membrane shrinkage. Elevated ROS levels and apoptosis shown by DCFDA and acridine orange-ethidium bromide staining revealed greater melanoma cell death by liposomes compared to free drug. Incorporating NIC liposomes into the thermogel system restricted the liposomes as a depot onto the upper skin layers. Sustained zero order release up to 48 h with liposomes and 23.58-fold increase in viscosity led to the sol-to-gel transition at 33℃ was observed with liposomal thermogel. Ex vivo gel permeation studies revealed that C-6 loaded liposomes incorporated within the thermogel successfully formed a depot over the upper skin layer for 6 h to prevent transdermal delivery and systemic adverse effects. Thus, it could be concluded that NIC loaded liposomal thermogel system could be an efficacious therapeutic alternative for the management of melanoma.

Tuning Mesoporous Silica Nanoparticles in Novel Avenues of Cancer Therapy.

The global menace of cancer has led to an increased death toll in recent years. The constant evolution of cancer therapeutics with novel delivery systems has paved the way for translation of innovative therapeutics from bench to bedside. This review explains the significance of mesoporous silica nanoparticles (MSNs) as delivery vehicles with particular emphasis on cancer therapy, including novel opportunities for biomimetic therapeutics and vaccine delivery. Parameters governing MSN synthesis, therapeutic agent loading characteristics, along with tuning of MSN toward cancer cell specificity have been explained. The advent of MSN in nanotheranostics and its potential in forming nanocomposites for imaging purposes have been illustrated. Additionally, various hurdles encountered during the bench to bedside translation have been explained along with potential avenues to circumvent them. This also opens up new horizons in drug delivery, which could be useful to researchers in the years to come.

Nanotechnology based drug delivery systems: Does shape really matter?

As of today, the era of nanomedicine has brought numerous breakthroughs and overcome challenges in the treatment of various disorders. Various factors like size, charge and surface hydrophilicity have garnered significant attention by nanotechnologists. However, more exploration in the field of nanoparticle shape and geometry, one of the basic physical phenomenon is required. Tuning nanoparticle shape and geometry could potentially overcome pitfalls in therapeutics and biomedical fields. Thus, in this article, we unveil the importance of tuning nanoparticle shape selection across the delivery platforms. This article provides an in-depth understanding of nanoparticle shape modulation and advise the researchers on the ideal morphology selection tailored for each implication. We deliberated the importance of nanoparticle shape selection for specific implications with respect to organ targeting, cellular internalization, pharmacokinetics and bio-distribution, protein corona formation as well as RES evasion and tumor targeting. An additional section on the significance of shape transformation, a recently introduced novel avenue with applications in drug delivery was discussed. Furthermore, regulatory concerns towards nanoparticle shape which need to be addressed for harnessing their clinical translation will be explained.

Biomimetic nanotherapeutics: Employing nanoghosts to fight melanoma.

Melanoma is a cancer of melanocytes present at the basal layer of the skin. Nanomedicine has armed us with competent platform to manage such fatal neoplastic diseases. Nevertheless, it suffers from numerous pitfalls such as rapid clearance and opsonization of surface-functionalized carriers, biocompatibility and idiopathic reactions which could be difficult to predict in the patient. Biomimetic approach, a novel step towards personalized medicine bridges these drawbacks by employing endogenous cell membranes to traverse physiological barriers. Camouflaged carriers coated with natural cell membranes possess unique characteristics such as high circulatory periods, and the absence of allogenic and xenogenic responses. Proteins residing on the cell membranes render a diverse range of utilities to the coated nanoparticles including natural efficiency to identify cellular targets, homologous targeting, reticuloendothelial system evasion, biocompatibility and reduced adverse and idiopathic effects. In the present article, we have focused on cell membrane camouflaged nanocarriers for melanoma management. We have discussed various types of biomimetic systems, their processing and coating approaches, and their characterization. We have also enumerated novel avenues in melanoma treatment and the combination of biomimetic systems with smart nanoparticulate systems with the potential to bring breakthroughs in the near future. Additionally, immunotherapy-based biomimetic systems to combat melanoma have been highlighted. Hurdles towards clinical translation and ways to overcome them have been explained in detail.