Biodegradable concanavalin A functionalized polycaprolactone nanoparticle: A promising avenue for cancer therapy.

OBJECTIVE: Receptor-based tumor-selective delivery of therapeutic efficacy and therapeutic index of cytotoxic drugs that exhibit dose-limiting toxicity is observed. Concanavalin A (Con A) was selected as the ligand for the proposed system, which was appended to the polycaprolactone nanoparticles (NPs) carrying the drug to be a very efficient approach for the treatment of cancer. METHODS: Preparation of plain polycaprolactone nanoparticles was carried out employing the emulsion diffusion evaporation technique. Con A was conjugated using carbodiimide chemistry by coupling -COOH group on the surface of nanoparticles. The paclitaxel-loaded Con A-conjugated nanoparticles were further subjected to the characterization of various parameters, that is, surface morphology, particle size, and polydispersity index. In vitro drug release study of both the formulations (plain & conjugated) was done using a dialysis tube up to 48 h in phosphate buffer (pH 7.4). RESULTS: Studies done in xenograft models evidently propose a dose-dependent cytotoxicity response, that is, shrink in % cell growth with increase in the concentration of the drug. The fluorescence photomicrograph clearly revealed the access of the Con A-conjugated nanoparticles to the tumor. A noteworthy biodistribution difference of the paclitaxel from prepared systems was observed. At the same time, Con A-coupled nanoparticles increased the accumulation of paclitaxel in the tumor cells. CONCLUSIONS: Hence, the Con A-conjugated nanoparticles formulation as compared to uncoupled solid lipid nanoparticles formulation and free drug solution showed nearly two times higher uptake because of the lectin receptors on the surface of tumors. Hence, it was envisaged to design polymeric nanoparticles which would be administered intravenously for better therapeutic efficacy.

An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations.

ETHNOPHARMACOLOGICAL RELEVANCE: The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2. AIM OF THE REVIEW: Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations. MATERIAL AND METHOD: The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as "SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation" were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 15.0.0.160 (PerkinElmer Informatics, Inc.). RESULT: A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases. CONCLUSION: According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.

An Insight into Anticancer Bioactives from Punica granatum (Pomegranate).

Cancer is one of the major reasons for mortality across the globe. Many side-effects are associated with the formulations available in the market, affecting the quality of life of the patients. This has caused the researchers to find an alternative source of medications, such as herbal medicine, showing a promising effect in anticancer treatment; one such source is Pomegranate, which belongs to the family Punicaceae. Punica granatum contains many polyphenols that have antioxidant, antidiabetic, and therapeutic effects in the treatment and management of metabolic and cardiovascular diseases, as well as a favourable effect on anticancer therapy. Polyphenols like punicalin, punicalagin, and ellagic acid are a few of the many compounds responsible for the anticancer activity of pomegranate. Many preparations of pomegranate, such as Pomegranate Juice (PJ), Pomegranate Seed Oil (PSO), Pomegranate peel extract (PoPx), etc. are used in various clinical studies. These polyphenols show anticancer activity by either arresting the cell cycle in the G2/M phase, inducing apoptosis or damaging the DNA of tumor cells. This review explicitly discusses the role and mechanism of bioactives obtained from the pomegranate in the treatment and management of cancer. The chemical structure, properties, and role of pomegranate in the treatment of breast, lung, thyroid, colon, and prostate cancer have been focused on in detail. This review also discusses various targeted drug delivery approaches for tumour treatment as well as patented preparation of pomegranate compounds along with the ongoing clinical trials.

Lipid-Based Nanocarriers for Lymphatic Transportation.

The effectiveness of any drug is dependent on to various factors like drug solubility, bioavailability, selection of appropriate delivery system, and proper route of administration. The oral route for the delivery of drugs is undoubtedly the most convenient, safest and has been widely used from past few decades for the effective delivery of drugs. However, despite of the numerous advantages that oral route offers, it often suffers certain limitations like low bioavailability due to poor water solubility as well as poor permeability of drugs, degradation of the drug in the physiological pH of the stomach, hepatic first-pass metabolism, etc. The researchers have been continuously working extensively to surmount and address appropriately the inherent drawbacks of the oral drug delivery. The constant and continuous efforts have led to the development of lipid-based nano drug delivery system to overcome the aforesaid associated challenges of the oral delivery through lymphatic transportation. The use of lymphatic route has demonstrated its critical and crucial role in overcoming the problem associated and related to low bioavailability of poorly water-soluble and poorly permeable drugs by bypassing intestinal absorption and possible first-pass metabolism. The current review summarizes the bonafide perks of using the lipid-based nanocarriers for the delivery of drugs using the lymphatic route. The lipid-based nanocarriers seem to be a promising delivery system which can be optimized and further explored as an alternative to the conventional dosage forms for the enhancement of oral bioavailability of drugs, with better patient compliance, minimum side effect, and improved the overall quality of life.

Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment.

A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0.04, +23.4 ± 0.3 mV and 88.3 ± 0.2% (PTX), and 89.6 ± 0.5% (DOX) respectively. In vitro drug release study of optimized formulation was carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed 75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s) were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest GI50 value of FA-D-P NLCs which was 1.04 ± 0.012 µg/ml, followed by D-P NLCs and D-P solution with GI50 values of 3.12 ± 0.023 and 3.89 ± 0.007 µg/ml, respectively. Findings indicated that the folic acid-conjugated PTX and DOX co-loaded NLCs exhibited lower GI50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.

Release promoter-based systematically designed nanocomposite(s): a novel approach for site-specific delivery of tumor-associated antigen(s) (TAAs).

The aim of present approach was to design and develop mannose functionalized reverse polymeric nanocomposite(s) system based on release promoter (MRPRPNs). Thus, the composition of the present formulation was optimized by employing the systematic design of experiments (DoE) for screening and optimization using L8-Array Taguchi and 3-level-3-factor Box-Behnken Design (BBD). Further, the developed formulation was observed for its preferential internalization by professional antigen presenting cells (macrophages/dendritic cells) and prompt release of loaded antigen in a pH-dependent manner. The optimized formulation was also extensively characterized for average hydrodynamic diameter, surface potential, poly dispersity index of reverse polymeric nanocomposite(s) which were recoded to be 189.4 ± 8.52 nm, 0.111 ± 0.024, -23.4 ± 2.0 mV, respectively; while percentage entrapment efficiency of OVA in MRPRPNs to be 60.17 ± 2.41%. The release pattern of OVA from MRPRPNs was consistent at pH 7.4. However, at acidic pH (≈5.5) where in protons (H+) are in-filtered into the core of MRPRPNs thereby generating the pressure, resultantly causing and creating the pores or disruption of the system thus allowed a prompt release (≈60-70%) of encapsulated OVA from interior to outer milieu within 1 h. MRPRPNs were preferentially internalized through receptor-mediated endocytosis and released the loaded OVA into the cytosol of RAW 264.7 cells. From the above findings, it can be concluded that reverse polymeric system could significantly be loaded with immunobioactive(s) and could potentially deliver the contents at the specific site for the better therapeutic outcome.

C-Type lectin receptor(s)-targeted nanoliposomes: an intelligent approach for effective cancer immunotherapy.

AIM: The purpose of present approach is to target C-Type lectin (CTL) receptors for preferential uptake by the macrophages/dendritic cells and improving the cross-presentation of ovalbumin. MATERIALS & METHODS: Conventional and engineered nanoliposomes (MPNLs) were fabricated and extensively characterized. The nanoliposome(s) was spherical in shape; and their ζ potential, size and ovalbumin loading efficiency were recorded to be 268 ± 4.15 nm, 23.4 ± 0.35 mV, 46.65 ± 1.84%, respectively. RESULTS: The findings demonstrate that MPNLs significantly improved the antigen uptake and its cross-presentation to evoke Th CD8+ cell-mediated cellular immunity. CONCLUSION: In a nutshell, this engineered approach mannose surface modification for active targeting to dendritic cells/macrophages and pH-dependent quick endosomal antigen release is a promising system for efficient cancer immunotherapy.

Theranostic Nanomedicine; A Next Generation Platform for Cancer Diagnosis and Therapy.

In the recent years, theranostic nanomedicine based strategies have gained much attention in the field of oncology particularly, in the development of new generation cancer diagnostic and therapeutic tools. Today, various approaches have been developed for bioactive(s) targeting to predefined pathological sites, as well as for quantification of physiological processes and visualization. Significant attempts have been made to combine therapeutic and diagnostic properties in to a single effective nanomedicine formulation. This concept, coined as "theranostics" is smart nanosystem(s), able to diagnose, bioactive(s) delivery and monitoring of therapeutic response. By combining therapeutic functionalities with molecular imaging, theranostic based strategies may be beneficial in the selection of therapy, planning of treatment, monitoring of objective response and planning of follow-up therapy based on the specific molecular characteristics of a disease. In this manuscript, we reviewed the recent development of theranostic approaches, various nanosystems as theranostic agents and applications of theranostic in cancer therapeutics and diagnostics.

Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin.

The purpose of the present investigation was to investigate the drug targeting potential of glycyrrhizin (GL) conjugated dendrimers (GL-PPI) and multi walled carbon nanotubes (GL-MWCNTs) towards liver targeting of a model anti-cancer agent, doxorubicin (DOX). The synthesis was confirmed by FTIR, 1H-NMR and morphology analysis. Higher DOX loading was observed in case of GL-PPI-DOX and GL-MWCNT-DOX (43.02 ± 0.64% and 87.26 0.57%, respectively) than parent nanocarriers. GL attachment considerably reduced the haemolytic toxicity of DOX by 12.38 ± 1.05 and 7.30 ± 0.63% by GL-PPI-DOX and GL-MWCNT-DOX, respectively. MTT cytotoxicity studies, flow cytometry and cell morphology assessment was done in HepG2 cell. The IC50 of DOX was reduced from 4.19±0.05 µM to 2.0±0.01 and 2.7±0.03 µM, respectively by GL-PPI-DOX and GL-MWCNT-DOX, respectively. Flow cytometry and phase contrast microscopy confirmed GL conjugated formulations to be significantly dragging higher cancer cell number of cells in early apoptosis as well as in early apoptotic phase.

Nanocarriers: a versatile approach for mucosal vaccine delivery.

Infectious agents generally use mucosal surfaces as entry port to the body thereby necessitating the need of development of mucosal vaccine as vaccination is important for disease avoidance and suppression. Vaccination through mucosal route is a promising strategy to elicit efficient immune response as parentally administered vaccines induce poor mucosal immunity in general. Safety, economy and stability are highly desired with vaccines and this can be achieved with use of delivery cargos. This review focuses on challenges related with mucosal vaccines and use of nanocarriers as suitable cargos to cater the antigen effectively to the desired site. The review also includes different factors which are to be considered regarding the performance of the nanocarriers and clinical status of these systems.

Dendritic cell-based vaccine research against cancer.

Therapeutic vaccines that treat cancers with the help of the patient's own immune system signify a feasible option for active immunotherapy against the disease. Dendritic cells (DCs) play a central role in modulating the immune response and thus can be wisely utilized as an immunotherapeutic strategy for cancer regimens. Advances in the knowledge of DC biology and function have led to the development of DC-based vaccines for cancer therapy. In the present review, we discuss the biology and function of DCs, their subsets and receptors, antigen loading and route of administration of DC vaccines, as well as active and passive targeting strategies for treating the cancer. We also discuss the preclinical and clinical status of these newly developed vaccines. Special attention should be given by the scientific community to the challenges that need to be solved for the successful implication of these vaccines in cancer therapy.

Polymer nanotechnology based approaches in mucosal vaccine delivery: challenges and opportunities.

Mucosal sites serve as the main portal for the entry of pathogens and thus immunization through mucosal routes can greatly improve the immunity. Researchers are continuously exploring the vaccination strategies to engender protective mucosal immune responses. Unearthing of mucosal adjuvants, that are safe and effective, is enhancing the magnitude and quality of the protective immune response. Use of nanotechnology based polymeric nanocarrier systems which encapsulate vaccine components for protection of sensitive payload, incorporate mucosal adjuvants to maximize the immune responses and target the mucosal immune system is a key strategy to improve the effectiveness of mucosal vaccines. These advances promise to accelerate the development and testing of new mucosal vaccines against many human diseases. This review focuses on the need for the development of nanocarrier based mucosal vaccines with emphases on the polymeric nanoparticles, their clinical status and future perspectives. This review focuses on the need and new insights for the development of nanoarchitecture governed mucosal vaccination with emphases on the various polymeric nanoparticles, their clinical status and future perspectives.

Novel strategies for effective transdermal drug delivery: a review.

Skin is the largest and easily accessible organ of the body and therefore can be extensively used as a prominent route of delivery for local and systemic effects. Though it presents a multifunctional barrier between body and surrounding particles, there are chances to deliver therapeutic nanocarrier, particularly in diseased skin. Both for dermal and transdermal drug delivery, the horny layer, i.e., the uppermost layer of the skin serve as the most resistant layer to be crossed and for this purpose, different perforation techniques are used that relatively widen the skin opening and allow the passage of drug (≤ 10 mg) and micromolecules, but this amateur disruption of the skin can be avoided in order to preserve this barrier against cutaneous microbiota by using deformable nanocarriers. In this review, we discuss the nanosized aggregates and microneedle technology for the advanced delivery of vaccines, protein, peptides, nucleic acid, and hormone across the skin.

Dendrimer, liposomes, carbon nanotubes and PLGA nanoparticles: one platform assessment of drug delivery potential.

Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70 ± 4.9%) followed by nanoparticles (DTX-NP, 62.34 ± 1.5%), liposome (49.2 ± 1.51%), and dendrimers (28.26 ± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC50 value of 1,235.09 ± 41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC50 values of 1,571.22 ± 151.27, 1,653.98 ± 72.89, 1,922.75 ± 75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48 ± 0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22 ± 0.48%; DTX-LIP, 4.13 ± 0.19%; DTX-NP, 6.43 ± 0.44%; DTX-CNTs, 14.87 ± 1.69%).