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Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints with no permanent cure. Although, there are some treatment strategies for RA that can go into remission but a precise treatment strategy is not currently available due to different patient manifestations. In addition, the use of various naturally available anti-inflammatory agents and antioxidants are hampered due to their instability in blood and lack of effective penetration into the synovial fluid. In this study, we aimed to enhance the therapeutic potential of natural but less bioavailable flavonoids by using lipid-based nanocarriers. Three types of lipid nanocarriers including stearic acid (SA), stearic-lauric (SL), and lecithin-chitosan (LC) nanocarriers (with encapsulated naringenin) were prepared by hot melt encapsulation and coprecipitation techniques, respectively. Arthritis in rats was induced by a single injection of complete Freund's adjuvant (CFA) in the sub-planter region of the left hind paw. Thirty six (36) male albino rats were divided into six groups with six animals each. Sole naringenin (NAR) and NAR-loaded lipid NPs (40 mg/kg) were administered orally to treatment groups after 1 h of CFA injection for 28 days continuously. NAR-loaded nanocarriers of spherical shape were synthesized with an average size less than ∼190 nm and zeta potential ( +30 mV for LC). We observed the encapsulation efficiency (EE) of 85%, 78% and 81% for LC, SA and SL, respectively. In vitro release of NAR from all nanoformulations showed sustained release behaviour. NAR loaded all lipid nanoformulations significantly (p

This study was designed to enhance solubility of dexibuprofen, an NSAID drug used to treat moderate to severe pain, by fabricating first generation, carbonate type nanosponges of β-CD. Novel chain-growth polycondensation method was used for the first time for preparation of the β-CD nanosponges. The results exhibited 6.3-fold enhancement of dexibuprofen solubilization which is higher than previously reported β-CD formulations. The particle size of nanosponges was 275.1 ± 28.5 nm and suitable negative zeta potential indicated formation of stable nanosponges. The formation of a new polymeric network in nanosponges and interaction of dexibuprofen with nanosponges were confirmed by FTIR and DSC/TGA studies. PXRD analysis also revealed the decline in crystallinity of dexibuprofen due to its complexation with nanosponges which is desirable for complete solubilization of drugs. At pH 6.8, β-CD nanosponges exhibited swelling index of 3 whereas solubility was enhanced more than 3 times as compared to pure drug and 2 times as compared to dexibuprofen loaded β-CD complexes. In-vitro release studies exhibited 89% drug release within 30 min at pH 6.8 with β-CD nanosponges. Dexibuprofen release at pH 1.2 was remarkably slower yet β-CD nanosponges showed superior dissolution as compared to β-CD or pure drug. Acute oral toxicity studies in rats exhibited no sign of illness, mortality, adverse clinical signs and toxicologically relevant changes in hematology, clinical biochemistry and histological findings. Thus, β-CD nanosponges prepared by optimized condensation method may be superior to other nano-formulation of β-CD to improve oral administration of lipophilic drugs such as dexibuprofen.

Folic acid is often used for active targeting of tumor cells to enhance therapeutic outcomes. Here, folic acid was conjugated with chitosan and folate-conjugated chitosan-lipid hybrid nanoparticles were prepared by ionic gelation method using anionic lipid. These nanoparticles were in size range of 200 to 400 nm with spherical shape. In vitro drug release data suggested a sustained release of cisplatin. The therapeutic efficacy of the folate-conjugated hybrid nanoparticles was evaluated in SK-OV-3, A2780 and MCF-7 cancer cell lines. A significant increase in cytotoxicity was observed with folate targeted LPHNPs compared to non-targeted LPHNPs. Significantly enhanced cellular uptake and cell cycle arrest resulting from folate-targeted nanoparticles were confirmed using fluorescence microscopy and flow cytometry. The therapeutic efficacy and tumor penetration were further evaluated in 3D spheroid tumor models. These studies suggest that folate-conjugated lipid-chitosan nanoparticles could enhance therapeutic activity and may represent a promising platform for active targeting of tumor cells.

Synthesis of carbon dots (CDs) or carbon quantum dots (QCDs) from different carbon sources have attracted much attention due to their excellent potential to advance wide range of applications such as biosensing, bioimaging, photoscience and other biomedical usage. However, the interaction of CDs (without any complex surface functionalities) with different cell lines especially with respect to their surface charge still needs to be elaborated in certain phenomena i.e. cytotoxicity, cellular uptake and inflammatory profiling. In this study, two oppositely charged CDs were synthesized and compared for their surface charge dependent interaction with different cell lines. Positively charged CDs were synthesized by using bovine serum albumin (BSA) and negatively charged CDs were synthesized using citric acid (CA) by acidic hydrolysis and reflux methods, respectively. Using both CDs, a concentration dependent cytotoxicity was carried out on 3T3 fibroblast, MDA-MB-231 breast cancer and RAW 264.7 macrophage cell lines, while cellular uptake and inflammatory studies were conducted with RAW 264.7 macrophages cell line. Results showed that both BSA and CA-CDs were not cytotoxic up to 400 μg/mL. Flow-cytometry studies indicated that cellular uptake of negatively charged CA-CDs was quite higher (~6.25%) than that of positively charged BSA-CDs (~1.24%). On the other hand, positively charged BSA-CDs have significantly enhanced the inflammatory cytokines release by RAW 264.7 macrophages cells. A concentration dependent increase in tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) was observed when RAW 264.7 macrophages cells were treated with BSA-CDs. In comparison, CA-CDs did not show any effect on these cytokines release. Therefore, it was concluded that the interaction of CDs with different cells is dependent on their surface charge which can also control their cellular influx and release of inflammatory cytokines.

In this study, polymeric blend microparticles are prepared with tunable drug releasing behavior, imparted by using poly(e-caprolactone) (PCL) as hydrophobic and hydroxypropyl methylcellulose (HPMC) as hydrophilic biodegradable polymeric constituents. Microparticles were prepared by simple oil in water emulsion-solvent evaporation method and evaluated for their sustained release profile by using nifedipine (half-life is about 2 h) as model drug. Hydrophilic PCL is added to optimize the drug release in simulated aqueous body fluid. Polyvinyl alcohol (PVA), used as emulsifier, was found to improve shape while HPMC increased surface smoothness of microparticles. High encapsulation efficiency was achieved, controllable by HPMC concentration. In vitro dissolution studies in acidic and neutral pH showed sustained release profile for all formulations. Synthesized microparticles, provided control over hydrophobic drug release by changing the proportion of HPMC and PCL in formulation at both acidic and intestinal pH.