Design, development, and evaluation of CDK-4/6 inhibitor loaded 4-carboxy phenyl boronic acid conjugated pH-sensitive chitosan lecithin nanoparticles in the management of breast cancer.

Our main aim to design and develop a novel 4-carboxy phenyl boronic acid (4-CPBA) conjugated Palbociclib (PALB) loaded pH-sensitive chitosan lipid nanoparticles (PPCL) to enhance the anti-cancer efficacy of the PALB in in-vitro cell line studies by loading into 4-CPBA conjugated chitosan lipid nanoparticles. 4-CPBA was conjugated to chitosan by carbodiimide chemistry and formation of conjugate was confirmed by 1HNMR, ATR-FTIR spectroscopic techniques. Ionic-gelation method was used for the fabrication of PPCL and particles size, PDI, zeta potential were found to be 226.5 ± 4.3 nm, 0.271 ± 0.014 and 5.03 ± 0.42 mV. Presence of pH-sensitive biological macromolecule i.e. chitosan in the carrier system provides pH-sensitivity to PPCL and sustainedly released the drug upto 144 h. The PPCL exhibited approximately 7.2, 6.6, and 5-fold reduction in IC50 values than PALB in MCF-7, MDA-MB-231 and 4T1 cells. Receptor blocking assay concluded that the fabricated nanoparticles were internalized into MCF-7 cells might be through sialic acid-mediated endocytosis. PPCL caused extensive mitochondrial depolarization, enhanced ROS generation, apoptosis (DAPI nuclear staining, acridine orange/ ethidium bromide dual staining), and reduced % cell migration than pure PALB. It was concluded that the hybrid lipid-polymer nanoparticles provides an optimistic approach for the treatment of breast cancer.

Andrographolide-Soya-L-α-Phosphatidyl Choline Complex Augmented Solubility and Drug Delivery in Leishmania donovani, a Causative Agent for Cutaneous and Visceral Leishmaniasis.

The utility of andrographolide (AN) in visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) is limited owing to poor solubility, hindered permeation, and unstable structure under physiological conditions. The present study mainly focuses on synthesizing of andrographolide-Soya-L-α-phosphatidyl choline (ANSPC) complex in ethanol and its characterization using various spectral and analytical techniques. Results from FT-IR, 1H NMR, ROSEY, and in silico docking techniques suggest ANSPC complex formation due to inter-molecular interaction between the hydrophilic head of SPC and hydroxyl group of AN present at 24th position. ANSPC complex demonstrated the solubility of 113.93 ± 6.66 µg/mL significantly (P < 0.05) greater than 6.39 ± 0.47 µg/mL of AN. The particle size of ANSPC complex was found to be 182.2 ± 2.69 nm. The IC50 value of AN suspension (PBS, pH ~ 7.4) at 24, 48, and 72 h against Leishmania donovani (L. donovani) was noticed to be 32.76 ± 4.53, 20.87 ± 2.37, and 17.71 ± 3.06 µM/mL, respectively. Moreover, augmented aqueous solubility of ANSPC complex led to significant (P < 0.05) reduction in IC50 value, i.e., 25.02 ± 4.35, 11.31 ± 0.60, and 8.33 ± 2.71 µM/mL at 24, 48, and 72 h, respectively. The IC50 values for miltefosine were noted to be 9.84 ± 2.65, 12.13 ± 7.26, and 6.56 ± 0.61 µM/mL at similar time periods. Moreover, ANSPC complex demonstrated augmented cellular uptake at 24 h as compared to 6 h in L. donovani. We suppose that submicron size and phospholipid-mediated complexation might have endorsed the permeation of ANSPC complex across the plasma membrane of L. donovani parasite by transport mechanisms such as P-type ATPase. ANSPC complex warrants further in-depth in vivo studies under a set of stringent parameters for translating the product into a clinically viable form.

Thymoquinone-Loaded Essential Oil-Based Emulgel as an Armament for Anti-psoriatic Activity.

Essential oils consist of oxygenated structures of secondary metabolites of aromatic plants with anti-psoriatic activities. Tea tree oil (TTO) is an essential oil with good anti-microbial and anti-inflammatory properties, exhibiting reduced levels of IL-1, IL-8, and PGE 2. Thymoquinone (TMQ) is popular herb in traditional medicine with known therapeutic benefits in several diseases and ailments. The ternary phase diagram was prepared with the weight ratio of Smix (Tween® 80:Labrasol®): oil:water ratio for o/w emulsion preparation. The globule size was 16.54 ± 0.13 nm, and PDI around 0.22 ± 0.01 of the TTO-TMQ emulsion and found thermodynamically stable. The percentage drug content was found in the range of 98.97 ± 0.62 to 99.45 ± 0.17% with uniformity of the ThymoGel using Carbopol®. The extensive physicochemical properties were studied using different analytical techniques, and in vitro drug release was performed using Franz-diffusion apparatus. Anti-psoriatic activity of the formulations was studied using Imiquimod-induced psoriasis-like inflammation model in male Balb/c mice and parameters like PASI score, ear thickness, and spleen to body weight index were determined as well as histological staining, ELISA, skin compliance, and safety evaluation of TTO were performed. The combination of essential oils with TMQ shows synergistic activity and efficiently reduces the psoriasis disease condition.

Development and evaluation of targeting ligand-anchored CNTs as prospective targeted drug delivery system.

Our main investigation in the present research was to developt and evaluate targeting ligand-anchored multiwalled carbon nanotubes (MWCNTs) as prospective targeted drug delivery system, with a special focus on the MWCNTs surface functionalization (FA-PEG bis-amine functionalized, carboxylated MWCNTs). In vitro release of 5-fluorouracil (5-FU) was studied at pH 7.4 phosphate buffer and 5.5 acetate buffer, which displayed initial faster followed by sustained release up to 900 min. Further, 5-FU/FA-PEG bis amine-MWCNTs was found to be long circulating, prolonged half-life and increased drug accumulation in target tissue.

Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression.

The aim of the present study was to investigate the propensity of thiolated chitosan nanoparticles (TCNs) to enhance the nasal delivery of selegiline hydrochloride. TCNs were synthesized by the ionic gelation method. The particle size distribution (PDI), entrapment efficiency (EE), and zeta potential of modified chitosan (CS) nanoparticles were found to be 215 ± 34.71 nm, 70 ± 2.71%, and + 17.06 mV, respectively. The forced swim and the tail suspension tests were used to evaluate the anti-depressant activity, in which elevated immobility time was found to reduce on treatment. TCNs seem to be promising candidates for nose-to-brain delivery in the evaluation of antidepressant activity.

Drug targeting to arthritic region via folic acid appended surface-engineered multi-walled carbon nanotubes.

This study was aimed at developing and investigating folate anchored carbon nanotubes for targeting an anti-arthritic drug, Methotrexate (MTX) to inflammatory arthritic region. The folic acid (FA) was conjugated to amidated multi-walled carbon nanotubes (MWCNTs) and confirmed by Fourier transform infrared (FTIR), (1)H NMR spectroscopy and X-ray diffraction analysis. The MTX was loaded into the pristine and functionalized-MWCNTs and extensively characterized in vitro and in vivo studies. The drug entrapment efficiency was found high in folate conjugated MWCNTs. In vitro drug release in PBS (pH 7.4) from pristine MWCNTs and folate conjugated MWCNTs formulation was found to be 66.35 ± 2.3 and 56.88 ± 1.9% in 24 h, respectively. Folate conjugated MWCNTs significantly increased (p < 0.005) the percentage inhibition of arthritis, biological half-life and volume of distribution of MTX as compared to MTX-loaded naked MWCNTs as well as free MTX. In in vivo biodistribution studies, MTX was found to be significantly higher (p < 0.005) in arthritic joints from folate functionalized MWCNTs as compared to free drug as well as drug-loaded naked MWCNTs. The present outcomes highlights the propensity of drug-loaded functionalized MWCNTs to alter the pharmacokinetics as well as sustained and targeted drug delivery system as well.