New Insights into the Applications of 3D-Printed Biomaterial in Wound Healing and Prosthesis.

Recently three-dimensional bioprinting (3D-bioP) has emerged as a revolutionary technique for numerous biomedical applications. 3D-bioP has facilitated the printing of advanced and complex human organs resulting in satisfactory therapeutic practice. One of the important biomedical applications of 3D-bioP is in tissue engineering, wound healing, and prosthetics. 3D-bioP is basically aimed to restore the natural extracellular matrix of human's damage due to wounds. The relevant search was explored using various scientific database, viz., PubMed, Web of Science, Scopus, and ScienceDirect. The objective of this review is to emphasize interpretations from the pre-executed studies and to assess the worth of employing 3D-bioP in wound healing as well as prosthetics in terms of patient compliance, clinical outcomes, and economic viability. Furthermore, the benefits of applying 3D-bioP in wound healing over traditional methods have been covered along with the biocompatible biomaterials employed as bioinks has been discussion. Additionally, the review expands about the clinical trials in 3D-bioP field, showing promise of biomedical applicability of this technique with growing advancement in recent years.

Assessment of anti-arthritic activity of lipid matrix encased berberine in rheumatic animal model.

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model. The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimised through Box-Behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations. The optimised NLCs exhibited a mean diameter of 180.2 ± 0.31 nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27 mm, decline in paw withdrawal timing, and improvements in walking behaviour were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation. The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Progress in Polymeric Micelles as Viable Wagons for Brain Targeting.

Polymeric micelles have opened up new horizons for improving drug delivery to brain particularly due to their small size, long circulation time, good stability and targetability. They are used to treat a variety of brain conditions, including glioblastoma, migraine, Alzheimer's, Parkinson's, and other conditions linked to the brain. Micelles are currently underutilised in brain targeting despite having several benefits and spanning a wide variety of brain illnesses. Since most medications are unable to cross the blood brain barrier, scientists are continuously working to discover efficient solutions to the problems. The most pressing issue was thought to be the viability and difficulties of translating micelles into the therapeutic setting. This review describes the role of micellar delivery system in brain diseases treatment along with their route of administration and outcomes. The review also discusses the current state of patents and clinical trials in the relevant fields and their potential future applications.

QbD-assisted development of lipidic nanocapsules for antiestrogenic activity of exemestane in breast cancer.

Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.

Appraisal of anti-gout potential of colchicine-loaded chitosan nanoparticle gel in uric acid-induced gout animal model.

Present study is aimed at transdermal delivery of colchicine-loaded chitosan nanoparticles. The nanoformulations were prepared utilising spontaneous emulsification method and optimised through 23 factorial designs. The optimised formulation (CHNP-OPT) displayed an average particle size of 294 ± 3.75 nm, entrapment efficiency 92.89 ± 1.1% and drug content 83.45 ± 2.5%, respectively. In vitro release study demonstrated 89.34 ± 2.90% release over a period of 24 h. Further, CHNP-OPT incorporated into HPMC-E4M (hydroxypropyl methylcellulose) to form transdermal gel. CHNPgel displayed 74.65 ± 1.90% permeation and stability over a period of 90 days. The anti-gout potential of CHNPgel formulation was evaluated in vivo against monosodium urate (MSU) crystal-induced gout in animal model. There was significant reduction in uric acid level, during MSU administration, when compared with the conventional gel of colchicine. The enhanced therapeutic potential was witnessed through X-ray. The study revealed that colchicine-loaded CHNPgel proved their supremacy over plain colchicine and can be an efficient delivery system for gout treatment.

An Assessment of In-vitro and In-vivo Evaluation Methods for Theranostic Nanomaterials.

Nanoparticles (NPs) as nanocarriers have emerged as novel and promising theranostic agents. The term theranostics revealed the properties of NPs capable of diagnosing the disease at an early stage and/or treating the disease. Such NPs are usually developed employing a surface engineering approach. The theranostic agents comprise NPs loaded with a drug/diagnostic agent that delivers it precisely to the target site. Theranostics is a field with promising results in enhancing therapeutic efficacy facilitated through higher payload at the targeted tissue, reduced dose, and dose-dependent side effects. However, controversies in terms of toxicity and size-dependent properties have often surfaced for NPs. Thus, a stringent in-vitro and in-vivo evaluation is required to develop safe and non-toxic NPs as theranostic agents. The review also focuses on the various entry points of NPs in the human system and their outcomes, including toxicity. It elaborates the evaluation criteria to ensure the safe use of NPs for diagnostic and therapeutic purposes.

Assessments of in vitro and in vivo antineoplastic potentials of ß-sitosterol-loaded PEGylated niosomes against hepatocellular carcinoma.

ß-sitosterol (BS), a phytosterol, exhibits ameliorative effects on hepatocellular carcinoma (HCC) due to its antioxidant activities. However, its poor aqueous solubility and negotiated bioavailability and short elimination half-life is a huge limitation for its therapeutic applications. To overcome these two shortcomings, BS-loaded niosomes were made to via, film hydration method and process parameters were optimized using a three-factor Box-Behnken design. The optimized formulation (BSF) was further surface-modified with polyethylene glycol (PEG). The resulting niosomes (BSMF) have spherical shapes, particle sizes, 219.6 ± 1.98 nm with polydispersity index (PDI) and zeta potential of 0.078 ± 0.04 and -19.54 ± 0.19 mV, respectively. The drug loading, entrapment efficiency, and drug release at 24 h of the BSMF were found to be 16.72 ± 0.09%, 78.04 ± 0.92%, and 75.10 ± 3.06%, respectively. Moreover, BSMF showed significantly greater cytotoxic potentials on Hep G2 cells with an enhanced cellular uptake relative to pure BS and BSF. The BSMF also displayed potentially improved curative property of HCC in albino wistar rat. Thus, the BSMF could be one of the promising therapeutic modalities for HCC treatment in terms of targeting potential resulting in enhanced therapeutic efficacy.

Assessing the pharmacokinetics and toxicology of polymeric micelle conjugated therapeutics.

Introduction: Analogous to nanocarriers such as nanoparticles, liposomes, nano lipoidal carriers, niosomes, and ethosomes, polymeric micelles have gained significance in the field of drug delivery. They have attracted scientists worldwide by their nanometric size, wide range of polymers available for building block synthesis, stability and potential to enhance the targeting and safety of drugs. Incorporation of drugs within the interior of polymeric micelles alters the drug pharmacokinetics, which generally results in increased efficiency.Areas covered: This review deals with the pharmacokinetics of various anti-neoplastic drugs loaded into micelles. The structure of polymeric micelles, polymers employed in their development and techniques involved will be discussed. This is followed by discussion on the pharmacokinetics of anti-cancer drugs loaded into polymeric micelles and the toxicity concerns associated.Expert opinion: Polymeric micelles are nanometeric carriers, with higher stability, polymeric flexibility and higher drug loading of poorly water-soluble drugs. These nanosystems help in increasing the bioavailability of drugs by encapsulating them within the hydrophobic core. The proper selection and design of the amphiphilic polymer for micelles is a crucial step as it decides the toxicity and the biocompatibility.

Metal toxicity and natural antidotes: prevention is better than cure.

Toxicity due to heavy metals (HM), specifically mercury (Hg), arsenic (As), lead (Pb), and cadmium (Cd) remains a challenge to scientists till date. This review gives insights into natural antidotes for the management and prevention of HM toxicity. Various databases such as PubMed, Embase, and Science Direct were searched for available facts on natural antidotes and their commercial products against HM toxicity till date. Toxicity owing to such metals needs prevention rather than therapy. Natural antidotes, fruits and vegetables, rich in antioxidant are the answers to such toxicities. Synthetic chelators impart a major drawback of removing essential metals required for normal body function, along with the toxic one. Natural antioxidants are bestowed with scavenging and chelation properties and can be alternative for synthetic chelating agents. Natural compounds are abundantly available, economic, and have minimal side effects when compared with classical chelators. Prevention is better than cure and thus adding plentiful vegetables and fruits to our diet can combat HM toxicity-related illness. Graphical abstract.

Augmented Therapeutic Efficacy of Naringenin Through Microemulsion-Loaded Sericin Gel Against UVB-Induced Photoaging.

Naringenin (NAR) is a flavonoid found in citrus fruits such as grapes and oranges. Recently, NAR has demonstrated its potential in inhibition of photoaging. The aim of the present study was to investigate the efficacy of sericin (SR) gel loaded with NAR microemulsion (ME) to inhibit UVB-induced photoaging and prevention of epidermoid carcinoma in animal model. NAR -ME was prepared and optimized through Box-Behnken design. The optimized ME was loaded into sericin (SR) gel. The formulations were subjected to various in vitro, in vivo and cytotoxicity studies over A431 cell lines. The optimized ME revealed a globule size of 249.05 ± 3.78 nm, 6.7 ± 0.5 pH and 73.1 ± 2.11% release over a period of 24 h respectively. Cytotoxicity studies revealed a depression in IC50 value in NAR -ME (65.11 ± 1.54 µg/ml) when compared with NAR (118.1 ± 2.09 µg/ml). The NAR-ME-SR gel displayed enhanced therapeutic potential when compared with plain NAR, in terms of augmented antiproliferative activity. Graphical abstract.

Sericin: A Versatile Protein Biopolymer with Therapeutic Significance.

Sericin is a unique proteinaceous biopolymer obtained from cocoons of Bombyx Mori. It has become very popular since it is bestowed with numerous health benefits. Sericin is composed of 18 types of amino acids, out of which 8 amino acids play a significant role in human metabolic pathways. Sericin is easily amenable to make into novel dosage forms and also has been conferred with numerous therapeutic activities such as wound healing, antihypertensive, neuro-protective, antitumor, anti-diabetic, anti-wrinkle, anti-ageing and antioxidant amongst various others. This review summarizes the current status of sericin, as a therapeutic moiety with a focus on active constituents as well as their proposed mechanism in the treatment of various chronic diseases. It also summarizes previous and current in-vitro, in-vivo, cell lines studies and clinical trials based pieces of evidence corroborating the therapeutic activities of sericin.

Correction to: a facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

In the original article the blots for BAX were inadvertently flipped in Fig. 11a. The inadvertent error in the case of BAX does not change any of the results.

Biotin anchored nanostructured lipid carriers for targeted delivery of doxorubicin in management of mammary gland carcinoma through regulation of apoptotic modulator.

Mammary gland tumour has the highest incidence rate and mortality in women, worldwide. The present study envisaged a molecularly targeted nanostructured lipid carrier (NLCs) for doxorubicin (Dox) delivery capable of inducing cellular apoptosis in mammary gland tumour. NLCs were prepared utilizing Perilla frutescens oil (54-69% ω3-fatty acid) as liquid lipid to enhance entrapment of Dox through molecular ion pairing. Biotin decorated NLCs (b-Dox-NLCs) were evaluated in vitro and in vivo. The b-Dox-NLCs showed particle size of 105.2 ± 3.5 nm, zeta potential -35 ± 2 mV, entrapment 99.15 ± 1.71%, drug content 19.67 ± 2.6 mg.g-1, biotin content 5.85 ± 0.64 µg.g-1 and drug release 98.67 ± 2.43% (facilitated by acidic microenvironment) respectively. MTT assay and Flow cytometric analysis revealed higher anti-proliferative capability of b-Dox-NLCs to force apoptosis in MCF-7 cell line vis-à-vis marketed Dox, evidenced by reactive oxygen species level and mitochondrial membrane potential mediated apoptosis. Enhanced antitumor targeting, therapeutic safety and efficacy was exhibited by b-Dox-NLCs, as investigated through tumour volume, animal survival, weight variation, cardiotoxicity and biodistribution studies in 7,12-Dimethylbenz[a]anthracene induced mammary gland tumour. Immunoblotting assay demonstrated b-Dox-NLCs downregulated anti-apoptotic proteins, i.e. bcl-2, MMP-9 while upregulated pro-apoptotic proteins, i.e. caspase-9, p16 and BAX. The experimental results suggest that biotinylated ω3-fatty acid augmented NLCs loaded with Dox are capable of inducing programmed cell death in mammary tumour and can be utilized as safe and effective delivery system with enhanced potential for mammary gland carcinoma therapy.

Tamanu oil potentiated novel sericin emulgel of levocetirizine: repurposing for topical delivery against DNCB-induced atopic dermatitis, QbD based development and in vivo evaluation.

The present study was aimed at preparing and evaluating levocetirizine (LCZD) loaded emulgel containing tamanu oil and sericin for atopic dermatitis (AD) therapy. The emulgel envisaged topical delivery of LCZD utilising natural antioxidants for superior therapeutic outcomes when compared with other conventional therapy. Tamanu oil based microemulsion (ME) was optimised utilising Box-Behnken design (BBD). The OPT-ME displayed globule size 379.5 ± 2.33 nm, polydispersity index 0.284, drug loading 0.41 ± 0.01% w/w, entrapment efficiency 94.34 ± 2.11% w/w and drug release 86.24 ± 4.90% respectively over a period of 24 h. The optimised formulation (OPT-ME) was further incorporated into sericin gel to form emulgel (LSE). In vivo pharmacodynamic studies revealed enhanced therapeutic potential of emulgel in terms of reduced scratching frequency and erythema score when compared with conventional gel. The superior therapeutic potential was further witnessed through histopathological and biochemical studies. The emulgel can be an alternative appropriate dosage form for the treatment of AD.

In vitro and in silico molecular interaction of multiphase nanoparticles containing inositol hexaphosphate and jacalin: Therapeutic potential against colon cancer cells (HCT-15).

Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.

A synergistic approach for management of lung carcinoma through folic acid functionalized co-therapy of capsaicin and gefitinib nanoparticles: Enhanced apoptosis and metalloproteinase-9 down-regulation.

BACKGROUND: Lung cancer is one of the most lethal cancers and lacks effective treatment strategy. Therapeutic efficacy can be improved through active targeting approach utilizing surface engineered nanoparticles (NPs) for cancer therapy. PURPOSE: The present study envisioned development of Folic acid (FA) functionalized NPs for co-administration of gefitinib (Gnb) and capsaicin (Cap) respectively to enhance the therapeutic outcome by disabling the barriers related to tumors extracellular matrix. RESEARCH METHODS AND PROCEDURE: The FA conjugated Gnb/Cap polymeric (PLGA-PEG) NPs were prepared using oil in water emulsion technique and methodically developed using Quality by Design (QbD) concept employing central composite design. The developed formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. RESULTS: The modified NPs displayed particle sizes of 217.0 ±â€¯3.2 nm and 213.0 ±â€¯5.2 nm and drug release of 85.65 ±â€¯3.21% and 81.43 ±â€¯4.32% for Gnb and Cap respectively. Higher cellular uptake and lower cell viability in A549 cell line was displayed by functionalized NPs compared to free drug. Co administration of Gnb and Cap NPs displayed significant targeting potential, reduction in tumor volume while restoring the biochemical parameters viz., SOD, catalase, TBARS and protein carbonyl, towards normal levels when compared with toxic group. Significant down regulation was observed for anti-apoptotic proteins (MMP-9) and up regulation of pro-apoptotic proteins (caspase-3, caspase-9 and MMP-9) with co-therapy of Gnb and Cap NPs, when compared with individual therapy through Gnb/Cap. CONCLUSION: Potentiation of the action of Gnb when co administered with Cap NPs can be a promising breakthrough for developing safe, effective and targeted delivery for lung carcinoma therapy.

Pectin-encrusted gold nanocomposites containing phytic acid and jacalin: 1,2-dimethylhydrazine-induced colon carcinogenesis in Wistar rats, PI3K/Akt, COX-2, and serum metabolomics as potential targets.

Phytic acid (PA) has momentous chemotherapeutic potential. Due to the chelate formation and rapid elimination, it is not popular in cancer treatment. The present work was inquested to develop a surface-modified nanoformulation of PA which prevents its speedy elimination and maximizes chemotherapeutic action. Chloroauric acid was reduced with pectin to produce pectin-gold nanoparticles (PGNPs). PGNPs were incubated with PA and jacalin for drug loading and surface modifications, respectively, to form PA-loaded jacalin-pectin-gold nanoparticles (PA-J-PGNPs). Formulation(s) were assessed for various pharmaceutical/pharmacological parameters. To validate the efficacy against colon carcinogenesis, formulation(s) were assessed in 1,2-dimethylhydrazine (DMH)-treated Wistar rats. DMH treatment distorted colonic architecture, oxidative, and hemodynamic parameters, which were favorably restored by PA-J-PGNP administration. To further confirm our deliberations, formulation(s) were also examined against DMH-altered metabolic changes and expression of markers pertaining to cellular proliferation, which was reinstated by PA-J-PGNPs. Our findings establish PA formulation(s) as a promising approach for suppression of colon carcinogenesis.

A facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

Lung carcinoma ranks highest in cancer-related death (about 20% of total cancer deaths) due to poor prognosis and lack of efficient management therapy. Owing to the lack of effective therapeutic approaches, survival rate of less than 5 years persists over the years among non-small cell lung cancer (NSCLC) patients. Capsaicin (CAP) is well reported for its antiproliferative and antioxidant properties in various literature but lacks an appropriate delivery carrier. The present study was aimed to develop CAP-loaded hyaluronic acid (HA) nanoparticles (NPs) utilizing layer by layer technique to achieve enhanced and precise delivery as well as target specificity. The NPs were evaluated for in vitro release, particle size, zeta potential, and cytotoxicity on A549 cells. The optimized NPs exhibited a particle size of 194 ± 2.90 nm, - 27.87 ± 3.21 mV zeta potential, and 80.70 ± 4.29% release, respectively, over a period of 48 h. Flow cytometric analysis revealed superior performance of HA-PCL-CAP in terms of suppressed cell viability in A549 cell lines when compared with CAP and PCL-CAP. Further, HA-anchored NPs were evaluated in vivo for their therapeutic efficacy in urethane-induced lung carcinoma in rat model. The superlative therapeutic potential of HA-PCL-CAP was advocated from the results of reactive oxygen species and mitochondrial membrane-mediated apoptosis. HA-PCL-CAP-administered groups presented greater therapeutic efficacy as revealed through reduced tumor volume and improved animal survival rate. A greater drug accumulation in tumor tissue as revealed from biodistribution studies evidences targeting potential of HA-PCL-CAP in urethane-induced lung carcinoma. Graphical abstract ᅟ.