Pongamia pinnata seed extract-mediated green synthesis of silver nanoparticle loaded nanogel for estimation of their antipsoriatic properties.

This research describes the eco-friendly green synthesis of silver nanoparticles employing Pongamia pinnata seed extracts loaded with nanogel formulations (AgNPs CUD NG) to improve the retention, accumulation, and the penetration of AgNPs into the epidermal layer of psoriasis. AgNPs were synthesized using the Box-Behnken design. Optimized AgNPs and AgNPs CUD NG were physico-chemically evaluated using UV-vis spectroscopy, SEM, FT-IR, PXRD, viscosity, spreadability, and retention studies. It was also functionally assessed using an imiquimod-induced rat model. The entrapment efficiency of AgNPs revealed ~ 79.35%. Physico-chemical parameters announced the formation of AgNPs via surface plasmon resonance and interaction between O-H, C = O, and amide I carbonyl group of protein extract and AgNO3. Optimized AgNPs showed spherical NPs ~ 116 nm with better physical stability and suitability for transdermal applications. AgNPs CUD NG revealed non-Newtonian, higher spreadability, and better extrudability, indicating its suitability for a transdermal route. AgNPs CUD NG enhanced the retention of AgNPs on the psoriatic skin compared to normal skin. Optimized formulations exhibit no irritation by the end of 72 h, indicating formulation safety. AgNPs CUD NG at a dose of 1 FTU showed significant recovery from psoriasis with a PASI score of ~ 0.8 compared to NG base and marketed formulations. Results indicated that seed extract-assisted AgNPs in association with CUD-based NG formulations could be a promising nanocarrier for psoriasis and other skin disorders.

Effect of PEGylation on drug uptake, biodistribution, and tissue toxicity of efavirenz-ritonavir loaded PAMAM G4 dendrimers.

The present investigations aimed to compare the efficiency of PAMAM G4 (PG4) and PEGylated PAMAM G4 (PPG4) dendrimers as novel nanocarriers for the treatment of HIV-1. Synthesized PG4 and PPG4 dendrimers were confirmed by electrospray ionization and particle size with its morphology. The anti-human immunodeficiency virus (HIV) drug efavirenz (EFV) with a booster dose of ritonavir (RTV) was encapsulated into PG4 and PPG4 formerly noted as PG4ER and PPG4ER, respectively. Further, evaluated for dendrimers mediated solubilization, drug release, cytotoxicity, drug uptake, plasma, and tissue pharmacokinetics, and histopathology. PG4ER and PPG4ER both promoted a prolonged release of EFV in weakly acidic pH 4 up to 84 h and 132 h, respectively. The results of the cytotoxicity assay and drug uptake study showed that PPG4ER was safe and biocompatible up to 12.5 µg/ml. The plasma pharmacokinetic profile of EFV and RTV was significantly increased by PPG4ER with prolonged t1/2 up to three times as compared to free EFV-RTV and PG4ER. Histopathological analysis showed remarkably lower tissue toxicity in PPG4ER as compared to free EFV-RTV. Therefore, overall data suggested that PPG4 has a great potential for prolonged release of EFV and RTV with enhanced bioavailability and lower toxicity.

Improvement in Bioavailability and Pharmacokinetic Characteristics of Efavirenz with Booster Dose of Ritonavir in PEGylated PAMAM G4 Dendrimers.

Efavirenz (EFV) with a booster dose of ritonavir (RTV) (EFV-RTV) inhibits the metabolism of EFV and improves its bioavailability. However, inadequate organ perfusion with surface permeability glycoprotein (P-gp) efflux sustains the viable HIV. Hence, the present investigations were aimed to evaluate the pharmacokinetics and tissue distribution efficiency of EFV by encapsulating it into PEGyalated PAMAM (polyamidoamine) G4 dendrimers with a booster dose of RTV (PPG4ER). The entrapment efficiency of PEGylated PAMAM G4 dendrimers was found to be 94% and 92.12% for EFV and RTV respectively with a zeta potential of 0.277 mV. The pharmacokinetics and tissue distribution behavior of EFV within PPG4ER was determined by developing and validating a simple, sensitive, and reliable bioanalytical method of RP-HPLC. The developed bioanalytical method was very sensitive with a quantification limit of 18.5 ng/ml and 139.2 ng/ml for EFV and RTV, respectively. The comparative noncompartmental pharmacokinetic parameters of EFV were determined by administrating a single intraperitoneal dose of EFV, EFV-RTV, and PPG4ER to Wistar rats. The PPG4ER produced prolonged release of EFV with a mean residential time (MRT) of 24 h with Cmax 7.68 µg/ml in plasma against EFV-RTV with MRT 11 h and Cmax 3.633 µg/ml. The PPG4ER was also detected in viral reservoir tissues (lymph node and spleen) for 3-4 days, whereas free EFV and EFV-RTV were cleared within 72 h. The pharmacokinetic data including Cmax, t1/2, AUCtot, and MRT were significantly improved in PPG4ER as compared with single EFV and EFV-RTV. This reveals that the PPG4ER has great potential to target the virus harbors tissues and improve bioavailability.

Extraction, Isolation, Characterization, and Development of Phospholipids Complex Nanocarrier for Improved Solubility, Antiasthmatic, and Pharmacokinetic Potential of Curcuminoids.

BACKGROUND: Curcuma longa Linn. (Zingiberaceae) is a medicinal plant with significant biological activities owing to curcuminoids (CURs). Nevertheless, its low oral bioavailability because of low water solubility, inadequate absorption, short half-life, and rapid clearance hampered its clinical applications. OBJECTIVE: The study aimed to extract, isolate, characterize, and formulate the Phospholipon ®90H complex and evaluate for improved solubility, antiasthmatic and pharmacokinetic potential of CURs. METHODS: Phospholipon®90H-based complex of curcuminoids (CPLC) was synthesized via solvent evaporation technique and reported an improvement of solubility, antiasthmatic, and pharmacokinetic potential of CURs. CPLC was physico-chemically and functionally evaluated by Fourier transforms infrared spectroscopy, differential scanning calorimetry, powder x-ray diffractometry, oral bioavailability, and antiasthmatic activity. RESULTS: Ethyl acetate rhizome extracts (EARE) displayed ~17.42 % w/w extraction yield of CURs. CPLC revealed high entrapment of CURs (~ 92.55 % w/w) within the polar head of phospholipids. Small particle size ~ 194 nm with zeta potential value ~ -20.4 mV suggests the physical stability of CPLC. Physical analysis evidenced the formation of stable and amorphous CPLC by establishing hydrophobic and weak intermolecular forces between CURs and Phospholipon ®90H. Undoubtedly, the amorphous CPLC raised the aqueous solubility of CURs (~2-fold) compared to pure CURs. CPLC formulations (~ 20 mg/kg of CURs, p.o.) significantly lowered the leucocyte and eosinophil count compared to pure CURs. CPLC improved the oral bioavailability of CURs compared to pure CURs. CONCLUSION: Results highlight that CPLC could be established as a breakthrough respiratory nanocarrier for CURs and other phytocompounds with respiratory potential.

Biomedical applications of three-dimensional bioprinted craniofacial tissue engineering.

Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three-dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient-specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient-specific treatment plans and damage site-driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue-engineered skeletal muscle and the peripheral nervous system.

Bronchorelaxant, mast cell stabilizing, anti-inflammatory and antioxidant activity of Randia dumetorum (Retz.) Lamk. extracts.

Randia dumetorum (RD) fruits in different form have been ethnopharmacologically reported to possess antiasthmatic property. Therefore, present study was undertaken to evaluate two different extracts of RD i.e., ethyl acetate (RD-EA) and methanol (RD-ME) for bronchorelaxant, anti-inflammatory, mast cell stabilizing and antioxidant effect along with safety margin, according to OECD guidelines for toxicity. RD-ME and RD-EA (1 mg/mL) exhibited 68.75 and 57.39% inhibition of contraction against acetylcholine, while against histamine induced contraction, inhibition observed was 100 and 78.13%, respectively. Moreover, extracts attenuated the experimentally induced inflammation at 200 mg/kg with % inhibition of 41.62 by RD-ME and 30.36 by RD-EA in carrageenan model, while in egg albumin model RD-ME and RD-EA exhibited % inhibition of 48.31 and 33.75, respectively. In addition, RD-ME and RD-EA at 100 microg/mL demonstrated significant decrease in histamine release of 08.31 and 16.71 in C-48/80 induced mast cell degradation. RD extracts also exhibited antioxidant activity in DPPH, reducing power and metal chelation method, along with safe margin for oral administration as observed in acute toxicity evaluation.