Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

Abstract Lenalidomide (LND) is an anti-cancer drug and an effective derivative of thalidomide used for multiple myeloma therapy. Because of its poor solubility in water, LND is known to cause low oral bioavailability (below 33%), and as a direct consequence of this, the dosing frequency is extended thus increasing risk of toxicity. To improve its bioavailability and sustained release, the present study aims to formulate polymeric nanoparticles (NPs) for LND using [Poly (lactic-co-glycolic acid)] (PLGA) as a polymer. The polymeric NPs were evaluated for particle size, SEM, XRD, drug content, entrapment efficiency (EE), in vitro release studies and in vivo bioavailability studies in rats. The formulated NPs possessed a size of 179±0.9 nm and a zeta potential of -24.4 ± 0.2 mV. The drug loading and EE of the optimized formulation was 32 ± 0.37 % and 78 ± 0.92% respectively. After oral administration of LND PLGA-NPs, the relative bioavailability was enhanced about 3.67-fold compared to LND. This study demonstrates the novel drug delivery for LND with PLGA-NPs as effective drug delivery system for sustained delivery of LND

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

Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

Abstract Lenalidomide (LND) is an anti-cancer drug and an effective derivative of thalidomide used for multiple myeloma therapy. Because of its poor solubility in water, LND is known to cause low oral bioavailability (below 33%), and as a direct consequence of this, the dosing frequency is extended thus increasing risk of toxicity. To improve its bioavailability and sustained release, the present study aims to formulate polymeric nanoparticles (NPs) for LND using [Poly (lactic-co-glycolic acid)] (PLGA) as a polymer. The polymeric NPs were evaluated for particle size, SEM, XRD, drug content, entrapment efficiency (EE), in vitro release studies and in vivo bioavailability studies in rats. The formulated NPs possessed a size of 179±0.9 nm and a zeta potential of -24.4 ± 0.2 mV. The drug loading and EE of the optimized formulation was 32 ± 0.37 % and 78 ± 0.92% respectively. After oral administration of LND PLGA-NPs, the relative bioavailability was enhanced about 3.67-fold compared to LND. This study demonstrates the novel drug delivery for LND with PLGA-NPs as effective drug delivery system for sustained delivery of LND

Role of herbs at the crossroads of metabolic syndrome and mental illness

The potential use of herbs in treating and managing comorbidities is emerging. Mental illnesses (MIs) are a widespread cause of distress and dysfunction and substantially impact one's quality of life. While the precise reason for the onset of mental illness is elusive, several chronic health complications, including metabolic syndrome (MetS), affect an individual's well-being. Thus, it is beneficial to identify the intercepts and explore the role of herbs in combating MetS-associated MIs or vice versa. This study explores the relationship between Mets and mental illness and assesses which herbs may have properties that benefit both conditions. The research design and selection process were done among the mental disorder individuals with two sets of keywords and expanded controlled vocabulary phrases, nine databases for systematic literature searches, critical assessment of the papers obtained, and meta-analysis. Our findings suggest that the excess levels of inflammatory cytokines such as C-reactive protein, interleukin, and leptin resistance in MetS strongly correlate with MIs such as depression. The resulting cross-sectional pooled odds ratio was 1.75 (95% CI 1.60-1.92), indicating a strong relationship between Mets and MIs. This study provides an essential theoretical foundation for therapeutic options and prospective intervention methods for comorbid Mets and mental illness. Some herbs have a relevant effect in treating both cases, broadening the breadth of knowledge to guide future research on this topic

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

Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The standard treatment of DW care fails to address the prerequisites of treating DW owing to its multifactorial pathophysiology. Henceforth, developing a single treatment strategy to handle all the loopholes may effectively manage DW. The objective of the current study was to formulate Human beta defensin-2 (HBD-2) loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticle impregnated in collagen/chitosan (COL-CS) composite scaffolds for the accelerated healing of DW. Upon investigation, the developed biodegradable crosslinked scaffold possesses low matrix degradation, optimum porosity, and sustained drug release than the non-crosslinked scaffold. In vitro studies revealed that the HBD-2 COL-CS scaffold was biocompatible and accelerated cell migration and angiogenesis. The HBD-2 COL-CS scaffold showed significant antimicrobial activity in S. aureus, E. coli, and P. aeruginosa. The in vivo studies revealed that the HBD-2 COL-CS treated group accelerated healing compared to those in COL-CS and control groups. The ELISA results indicated a significant decrease in MMP-9, TNF-α, MPO, NAG, and NO with an increase in IL-10 in HBD-2 COL-CS treated group. The accelerated healing in HBD-2 COL-CS treated group might be due to the synergistic effects of PLGA (collagen synthesis and deposition and positive angiogenic effect), HBD-2 (anti-inflammatory, antibacterial, positive angiogenic effect, cell proliferation, and migration), COL (established wound healer and stabilizer) and CS (antibacterial, controlled drug release)

Role of herbs at the crossroads of metabolic syndrome and mental illness

129-140The potential use of herbs in treating and managing comorbidities is emerging. Mental illnesses (MIs) are a widespread cause of distress and dysfunction and substantially impact one's quality of life. While the precise reason for the onset of mental illness is elusive, several chronic health complications, including metabolic syndrome (MetS), affect an individual's well-being. Thus, it is beneficial to identify the intercepts and explore the role of herbs in combating MetS-associated MIs or vice versa. This study explores the relationship between Mets and mental illness and assesses which herbs may have properties that benefit both conditions. The research design and selection process were done among the mental disorder individuals with two sets of keywords and expanded controlled vocabulary phrases, nine databases for systematic literature searches, critical assessment of the papers obtained, and meta-analysis. Our findings suggest that the excess levels of inflammatory cytokines such as C-reactive protein, interleukin, and leptin resistance in MetS strongly correlate with MIs such as depression. The resulting cross-sectional pooled odds ratio was 1.75 (95% CI 1.60-1.92), indicating a strong relationship between Mets and MIs. This study provides an essential theoretical foundation for therapeutic options and prospective intervention methods for comorbid Mets and mental illness. Some herbs have a relevant effect in treating both cases, broadening the breadth of knowledge to guide future research on this topic

Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing

Background: Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The objective of the current study was to formulate Epidermal Growth Factor loaded Chitosan nanoparticle impregnated with thermos-responsive injectable hydrogel with protease inhibitor. EGF, shown in all stages of wound healing from inflammation to proliferation and remodelling, combined with Doxycycline, a well-known anti-inflammatory and anti-bacterial drug, could be a better strategy in diabetic wound healing. However, EGF’s low stability makes it difficult to use. Methodology: The nanoparticles were prepared using the ionic gelation method. The prepared nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, and SEM studies. Further, the optimized nanoparticle batch was loaded into hydrogel with a protease inhibitor. The hydrogel was evaluated for morphology, protease degradation, in vitro drug release, anti-bacterial activity, cell migration, in vitro cell biocompatibility, and in vivo wound healing studies. Results and Conclusion: The particle size analysis of nanoparticles revealed the size (203 ± 1.236 nm), Zeta potential (+28.5 ± 1.0 mV), and entrapment efficiency of 83.430 ± 1.8%, respectively. The hydrogel showed good porous morphology, injectability, thermo-responsive, biocompatibility, and controlled drug release. In vitro anti-bacterial studies revealed the potential anti-bacterial activity of doxycycline against various microbes. In vivo data indicated that combining EGF and DOX considerably reduced inflammation time-dependent than single-agent treatment. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis and a fully regenerated epithelial layer and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis, a fully regenerated epithelial layer, and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site