Correction to: Development of Methotrexate and Minocycline Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis.

Typesetting error occurred and author corrections to the numbering of figures and captions at the proofing stage were not incorporated in the published article.

Development of Methotrexate and Minocycline Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis is an autoimmune disease that leads to cartilage destruction, synovial joint inflammation, and bacterial joint/bone infections. In the present work, methotrexate and minocycline-loaded nanoparticles (MMNPs) were developed with an aim to provide relief from inflammation and disease progression/joints stiffness and to control the bacterial infections associated with rheumatoid arthritis. MMNPs were developed and optimized by solvent evaporation along with high-pressure homogenization technique using poly(lactic-co-glycolic acid) (50:50%) copolymer. FTIR spectrometric results showed the compatibility nature of methotrexate, minocycline, and poly(lactic-co-glycolic acid). The MMNPs showed particle size ranging from 125.03 ± 9.82 to 251.5 ± 6.23 nm with charge of around - 6.90 ± 0.8 to - 34.8 ± 4.3 mV. The in vitro release studies showed a sustained release pattern with 75.11% of methotrexate (MTX) release and 49.11% of minocycline hydrochloride (MNC) release at 10 h. The developed MMNPs were found to be stable at refrigerated condition and non-hemolytic nature (< 22.0%). MMNPs showed superior cytotoxicity for studied concentrations (0.1 to 1000 µM) compared with free MTX at both 24 and 48 h treatment period in a dose/time-dependent manner in inflammatory RAW 264.7 cells. Anti-bacterial studies indicate that the efficacy of the developed MMNPs to control infections was compared with pure MNC. In vivo anti-arthritis showed effective arthritis reduction potential of the developed MMNPs upon intravenous administration. This proof of concept implies that MTX with MNC combined nanoparticles may be effective to treat RA associated with severe infections. Graphical abstract.

Recent Progress in Stimuli-Responsive Intelligent Nano Scale Drug Delivery Systems: A Special Focus Towards pH-Sensitive Systems.

Stimuli-responsive nanocarriers are gaining much attention due to their versatile multifunctional activities, including disease diagnosis and treatment. Recently, clinical applications of nano-drug delivery systems for cancer treatment pose a challenge due to their limited cellular uptake, low bioavailability, poor targetability, stability issues, and unfavourable pharmacokinetics. To overcome these issues, researchers are focussing on stimuli-responsive systems. Nanocarriers elicit their role through endogenous (pH, temperature, enzyme, and redox) or exogenous (temperature, light, magnetic field, ultrasound) stimulus. These systems were designed to overcome the shortcomings such as non-specificity and toxicity associated with the conventional drug delivery systems. The pH variation between healthy cells and tumor microenvironment creates a platform for the generation of pH-sensitive nano delivery systems. Herein, we propose to present an overview of various internal and external stimuli-responsive behavior-based drug delivery systems. Herein, the present review will focus specifically on the significance of various pH-responsive nanomaterials such as polymeric nanoparticles, nano micelles, inorganic-based pH-sensitive drug delivery carriers such as calcium phosphate nanoparticles, and carbon dots in cancer treatment. Moreover, this review elaborates the recent findings on pH-based stimuli-responsive drug delivery systems with special emphasis on our reported stimuli-responsive systems for cancer treatment.

Combinatorial analysis of quercetin and resveratrol by HPTLC in Sesbania grandiflora/phyto-based nanoformulations.

A sensitive HPTLC method was developed for the simultaneous estimation of quercetin (QUR) and resveratrol (RES). The chromatographic separation was achieved using mobile phase toluene:chloroform:ethyl acetate:formic acid (3:2:4.9:0.1% v/v) and densitometric scan performed at 280 nm. The developed method was linear at 2-10 µg/mL with correlation coefficient of 0.9907 (QUR) and 0.9917 (RES). The method was validated for its precision, specificity, detection and quantification limits and % RSD was found to be less than 4.0%. The developed HPTLC method was evaluated in QUR and RES-loaded nanoformulation and Sesbania grandiflora leaf extract. The amount of QUR and RES present in the SG leaf extract was found to be 26.13 ± 0.7 µg/mg and 4.31 ± 0.8 µg/mg, respectively. The pH-dependent stability of RES has checked using the developed method. The above-developed method can be used to check the QUR/RES content in herbal/pharmaceutical formulation with scope towards industries.

In vivo synergistic anti-tumor effect of lumefantrine combined with pH responsive behavior of nano calcium phosphate based lipid nanoparticles on lung cancer.

Conventional treatment options for lung cancer treatment were restricted due to non-specific nature and side effects, with this associated problem and to overcome this we had developed lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF- CaP- Ls) affording pH sensitive mechanism. Herein, the present study the in vivo anti-cancer property of LF-CaP-Ls was checked in mice models. Further, reduced lung cancer progression of lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF-CaP-Ls) treated mice were assessed by measuring the 5-methyltetrahydrofolate (MTHF) in serum. Moreover, LF-CaP-Ls showed substantially a anticancer effect compared to that of lumefantrine loaded lipid nanoparticles (LF-Ls) and free lumefantrine (LF) by exhibiting higher effects in lung tumor bearing mice model as confirmed by reduced tumor progression. Histopathological examination of lungs supported with H&E staining proved the reduced tumor vasculature and reduced inflammatory cells for LF-CaP-Ls compared to that of free LF and LF-Ls. Further, visual inspection with acetic acid test confirmed the reduced tumor progression for LF-CaP-Ls compared to that of free LF and LF-Ls. Altogether, the overall results suggested that the developed LF-CaP-Ls may acts as a better therapeutic molecule for lung cancer due to its maintenance of increased level of 5-MTHF levels, reduced tumor weight. Further, hematological and biochemical parameters were measured and supports our in-vivo therapeutic effect of LF-CaP-Ls.

pH responsive delivery of lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the site specific treatment of lung cancer.

The present work aim to develop pH responsive nanosystem comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the effective treatment of lung cancer. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed developed LF-CaP-Cs were non crystalline in nature. The selected developed LF-CaP-Cs were in cubic phase with average particle size of 259.4 ± 19 nm with a charge of -2.28 ± 0.7 mV. The encapsulation efficiency for LF within LF-CaP-Cs was about 78.76 ± 0.5%. RP-HPLC analysis showed that LF release rate gets significantly enhanced with higher peak area at pH 4.0 compared to pH 5.0/pH 7.4. The in-vitro release of LF-CaP-Cs showed that LF release gets significantly increased at pH 4.0 (84.04 ± 0.4%) compared to pH 7.4 (48.32 ± 1.6%) at 12 h. Further, CAM assay showed the superior anti-angiogenesis potential of developed LF-CaP-Cs compared to LF-Cs/blank Cs. The cytotoxicity effect of LF-CaP-Cs (28 ± 1.8 µg/mL) was significantly higher than that of free LF (40 ± 0.9 µg/mL). The results of cellular uptake study proved the localization of LF at cellular level and AO/EB staining results revealed that the A549 cell undergoes apoptosis in A549 cells.