Biocorrosion and Cytotoxicity Studies on Biodegradable Mg-Based Multicomponent Alloys.

Magnesium-based multicomponent alloys with different compositions, namely Mg60Al20Zn5Cu10Mn5 (Mg60 alloy), Mg70Al15Zn5Cu5Mn5 (Mg70 alloy), and Mg80Al5Cu5Mn5Zn5 (Mg 80) alloys, were prepared using the disintegrated melt deposition technique. The DMD technique is a distinctive method that merges the benefits from gravity die casting and spray forming. This approach facilitates high solidification rates, process yields, and reduced metal wastage, resulting in materials with a fine microstructure and minimal porosity. Their potential as biodegradable materials was assessed through corrosion in different simulated body fluids (SBFs), microstructure, and cytotoxicity tests. It was observed that the Mg60 alloy exhibited low corrosion rates (~× 10-5 mm/year) in all SBF solutions, with a minor amount of corrosive products, and cracks were observed. This can be attributed to the formation of the Mg32(AlZn)49 phase and to its stability due to Mg(OH)2 film, leading to excellent corrosion resistance when compared to the Mg70 and M80 alloys. Conversely, the Mg80 alloy exhibited high corrosion rates, along with more surface degradation and cracks, due to active intermetallic phases, such as Al6Mn, Al2CuMg, and Al2Cu phases. The order of corrosion resistance for the Mg alloy was found to be ASS > HBSS > ABP > PBS. Further, in vitro cytotoxicity studies were carried out using MDA-MB-231 tumor cells. By comparing all three alloys, in terms of proliferation and vitality, the Mg80 alloy emerged as a promising material for implants, with potential antitumor activity.

Repigmentation of Segmental Vitiligo with Scalp and Pubic Follicular Unit Extraction Graft Transplantation.

Segmental vitiligo (SV) has been identified as a type of vitiligo starting early on in life with a rapidly progressive depigmentation in the affected area. Surgical modalities have shown better outcomes in SV compared with medical therapies. Perifollicular repigmentation being the mode of pigment spread after surgical treatments, follicular unit extraction graft surgery has shown complete repigmentation with minimal postoperative scarring. We present a case of SV where hair transplant surgery was done using scalp hair and pubic hair grafts at different times achieving complete repigmentation with photochemotherapy.

Role of Low-Level Light Therapy (LLLT) in Androgenetic Alopecia.

Androgenetic alopecia (AGA) is the commonest type of alopecia affecting over half of men and women. Only two drugs have been approved so far (minoxidil and finasteride), and hair transplant is the other treatment alternative. Low-level laser therapy (LLLT) has been claimed to be a new safe devise-based modality for stimulating hair growth in men and women in AGA. Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, and LLLT. Fifteen studies were found to be strongly relevant and were analyzed. Studies have shown that LLLT stimulated hair growth in both men and women. Studies with largest randomized controlled trials demonstrated statistically significant hair regrowth by terminal hair count in both males and females. One study also showed that LLLT and minoxidil had similar efficacy in hair growth and that combination therapy was even more effective. LLLT represents a non-invasive, safe, and potentially effective treatment option for patients with AGA who do not respond or are not tolerant to standard treatment of AGA. Moreover, combining LLLT with topical minoxidil solution and oral finasteride may act synergistic to enhance hair regrowth. However, the level of evidence of the studies is still low and hence more controlled large studies are needed.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy.

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.

Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells.

BACKGROUND: The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa). RESULTS: In this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines. CONCLUSIONS: Results showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs.

Poly (D,L-lactic-co-glycolide) nanoparticles for the improved therapeutic efficacy of all-trans-retinoic acid: a study of acute myeloid leukemia (AML) cell differentiation in vitro.

All-trans-retinoic acid reverses malignant cell growth and induces cell differentiation and apoptosis. Poor aqueous solubility and uncertain bioavailability are the limiting factors for using all-trans-retinoic acid for tumor therapy. The objective of present study was to encapsulate the hydrophobic drug all-trans-retinoic acid in the polymer poly (lactide-coglycolide). The encapsulation was expected to improve the bioavailability and solubility of the drug. Oil in water single emulsion solvent evaporation technique used for the preparation efficiently encapsulated about 60% of the drug. The drug release profile showed a biphasic pattern with 70% of the drug being released in first 48 hrs and the residual drug showing a slow controlled release reaching up to 8 days. The particle size of 150-200 nm as determined with TEM was ideal for tumor targeting. All-trans-retinoic acid loaded nanoparticles were efficient to induce differentiation and blocked the proliferation of HL-60 cells invitro. These studies also revealed that the dosage of drug required for the therapeutic effects have been reduced efficiently. Our studies thereby demonstrate that Poly (lactide-co-glycolide) based nanoparticles may be efficient for parenteral administration of the drug.

Scope of detection and determination of gallium(III) in industrial ground water by square wave anodic stripping voltammetry on bismuth film electrode.

Gallium(III) in ground water may cause human health hazards due to the antineoplastic and antimicrobial activities of gallium. However, the exposure limit of Ga(III) has not been set. This paper demonstrates the scope of employing the square wave anodic stripping voltammetry (SWASV) on bismuth film electrode (BiFE) for selective and sensitive detection of Ga(III) as well as its accurate and precise determination. The key parameters were optimized and the bismuth film morphology was characterized. The performance of BiFE was also compared with that of the mercury film electrode (MFE). The performance of BiFE was also studied for interferences of Zn(II), Cd(II), Tl(I) and Cu(II) ions. Gaussian peak fitting was performed to improve the calibration curve and the fitting process revealed almost similar stripping peak heights as obtained from the experimentally observed data though slight improvement in calibration was obtained from the peak area analysis. A good linear dynamic range (R(2)=0.996) was obtained in the concentration range of 20-100 µg/L with a limit of detection (LOD) of 6.6 µg/L (S/N=3) of Ga(III). A relative standard deviation of 2.9% (n=10) was obtained for 20 µg/L of Ga(III) solution. The practical analytical utility of the method was verified by the determination of Ga(III) in spiked water samples, where 100-105% recovery of Ga(III) was achieved.