PROTEUS SYNDROME: NEED FOR PATIENT CENTRIC THERAPY

Proteus syndrome (PS) is a hamartomatous disorder with multisystem involvement that results from mutation in the AKT1gene. Since the symptoms and severity of PS are unique to each patient, diagnosis and treatment become hard for the physician. This article is concentrated upon the identification and recognition of specific characteristics of the disease, pathophysiology, symptoms, diagnosis, treatment and the necessity of advanced diagnosis, effective generalized and personalized therapy, as well as the requirement of new drugs for the management of PS. Detailed studies on the PS and evidence from the case reports revealed the requirement of intensive care, accurate diagnosis, and an effective treatment for each patient preferably patient-centric drug delivery due to the high degree of variation in the symptoms and clinical features among patients

‘TRAIL’ of targeted colorectal cancer therapy

TRAIL, a tumor necrosis factor-related apoptosis-inducing ligand is a member of the tumor necrosis factor (TNF) superfamily, which is a cytokine that has shown a particularly precise and selective affinity towards death receptors that are overexpressed in cancer cells. While leaving the normal cells intact and unharmed, due to this property it has been the ligand of choice for highly precise cancer chemotherapeutic delivery system development. On numerous occasions, TRAIL has been used singularly and in combination with other drugs. It was observed that TRAIL had a tendency to be susceptible in terms of the cancer cells developing resistance against it. So TRAIL monotherapy was a bit of a rough patch for the molecule to become successful in the chemotherapy universe, however the conjugations and synergistic actions of TRAIL opened up new horizons which are discussed in this review with specific interest on colorectal cancer (CRC)

Understanding the implications of pharmaceutical excipients and additives in the treatment of diabetic foot ulcers

A diabetic foot ulcer (DFU) is a consequence of Diabetes Mellitus (DM) and involves complex pathological processes. Among diabetic patients DFU is a major cause of deaths resulting from the amputation of the lower limbs. Various treatment strategies have been developed for the treatment of DFUs, but to this date unfortunately no single treatment fulfills the prerequisites necessary for treating this condition due to its complex, multifactorial pathophysiology. Additionaly, costs associated with the treatment can be prohibitively high. Excipients are pharmaceutical agents which have diverse applications in the design of different dosage forms. Therefore, an ideal dosage form, with active excipients in combination or as adjuvants, which meet these requirements could be suited for treating DFUs. This review discusses the etiopathogenesis of DFUs and also the possible of the use of excipients and additives in various pathological cases of DFUs in designing medicinal products intended for the treatment of this condition

Understanding the implications of pharmaceutical excipients and additives in the treatment of diabetic foot ulcers

A diabetic foot ulcer (DFUs) is a consequence of Diabetes Mellitus (DM) and involves complex pathological processes. It is a major cause of deaths among diabetic patients as a result of amputations. Various treatment strategies have been developed for the treatment of DFUs; unfortunately no single treatment will fulfill the prerequisites necessary for treating DFUs due to its complexed, multifactorial pathophysiology and also the overall cost of these treatments are high. Excipients are the pharmaceutical agents which have diverse applications in the design of different dosage forms. Hence, an ideal dosage form, with active excipients in combination or as adjuvants, which meets these requirements would probably best suited for treating DFUs. This review discusses the etiopathogenesis of DFUs and also the possible use of excipients and additives on various pathological cases of DFUs in designing products intended for the treatment of DFUs

‘TRAIL’ of targeted colorectal cancer therapy

95-98TRAIL, a tumor necrosis factor-related apoptosis-inducing ligand is a member of the tumor necrosis factor (TNF) superfamily, which is a cytokine that has shown a particularly precise and selective affinity towards death receptors that are overexpressed in cancer cells. While leaving the normal cells intact and unharmed, due to this property it has been the ligand of choice for highly precise cancer chemotherapeutic delivery system development. On numerous occasions, TRAIL has been used singularly and in combination with other drugs. It was observed that TRAIL had a tendency to be susceptible in terms of the cancer cells developing resistance against it. So TRAIL monotherapy was a bit of a rough patch for the molecule to become successful in the chemotherapy universe, however the conjugations and synergistic actions of TRAIL opened up new horizons which are discussed in this review with specific interest on colorectal cancer (CRC)

WZB117 Decorated Metformin-Carboxymethyl Chitosan Nanoparticles for Targeting Breast Cancer Metabolism

The “Warburg effect” provides a novel method for treating cancer cell metabolism. Overexpression of glucose transporter 1 (GLUT1), activation of AMP-activated protein kinase (AMPK), and downregulation of mammalian target of rapamycin (mTOR) have been identified as biomarkers of abnormal cancer cell metabolism. Metformin (MET) is an effective therapy for breast cancer (BC), but its efficacy is largely reliant on the concentration of glucose at the tumor site. We propose a WZB117 (a GLUT1 inhibitor)-OCMC (O-carboxymethyl-chitosan)-MET combo strategy for simultaneous GLUT1 and mTOR targeting for alteration of BC metabolism. WZB117 conjugated polymeric nanoparticles were 225.67 ± 11.5 nm in size, with a PDI of 0.113 ± 0.16, and an encapsulation of 72.78 6.4%. OCMC pH-dependently and selectively releases MET at the tumor site. MET targets the mTOR pathway in cancer cells, and WZB117 targets BCL2 to alter GLUT1 at the cancer site. WZB117-OCMC-MET overcomes the limitations of MET monotherapy by targeting mTOR and BCL2 synergistically. WZB117-OCMC-MET activates AMPK and suppresses mTOR in a Western blot experiment, indicating growth-inhibitory and apoptotic characteristics. AO/EB and the cell cycle enhance cellular internalization as compared to MET alone. WZB117-OCMC-MET affects cancer cells’ metabolism and is a promising BC therapeutic strategy

Folic Acid Functionalized Diallyl Trisulfide–Solid Lipid Nanoparticles for Targeting Triple Negative Breast Cancer

DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against triple-negative breast cancer (TNBC). Its hydrophobicity, short half-life, lack of target selectivity, and limited bioavailability at the tumor site limit its efficacy in treating TNBC. Overexpression of the Folate receptor on the surface of TNBC is a well-known target receptor for overcoming off-targeting, and lipid nanoparticles solve the limitations of limited bioavailability and short half-life. In order to overcome these constraints, we developed folic acid (FA)-conjugated DATS-SLNs in this research. The design of experiment (DoE) method was employed to optimize the FA-DATS-SLNs’ nanoformulation, which resulted in a particle size of 168.2 ± 3.78 nm and a DATS entrapment of 71.91 ± 6.27%. The similarity index between MCF-7 and MDA-MB-231 cell lines demonstrates that FA-DATS-SLNs are more therapeutically efficacious in the treatment of aggravating TNBC. Higher cellular internalization and efficient Bcl2 protein downregulation support the hypothesis that functionalization of the FA on the surface of DATS-SLNs improves anticancer efficacy when compared with DATS and DATS-SLNs. FA-functionalized DATS-SLNs have demonstrated to be a promising therapeutic strategy for TNBC management

Lipid-based nanocarriers for breast cancer treatment - comprehensive review

Breast cancer is the second leading cancer-related disease as the most common non-cutaneous malignancy among women. Curative options for breast cancer are limited, therapeutically substantial and associated with toxicities. Emerging nanotechnologies exhibited the possibility to treat or target breast cancer. Among the nanoparticles, various lipid nanoparticles namely, liposomes, solid lipid nanoparticles, nanostructured lipid carriers and lipid polymer hybrid nanoparticles have been developed over the years for the breast cancer therapy and evidences are documented. Concepts are confined in lab scale, which needs to be transferred to large scale to develop active targeting nanomedicine for the clinical utility. So, the present review highlights the recently published studies in the development of lipid-based nanocarriers for breast cancer treatment