Search

In this work, we are comparing biomimetic niosomal nanoparticles (BNNs) with biomimetic liposomal nanoparticles (BLNs) and studying their drug carrier properties. A-BNNs and A-BLNs are prepared by lipid hydration method and characterized using DLS for size and zeta potential analysis, surface morphology by SEM, structural details by TEM, crystallinity and phase change by XRD, thermodynamic properties by DSC, TGA and DTGA, drug carrier properties by entrapment efficiency, drug release studies by open-end tube method and its mechanistic assessment by fitting with various models such as zero order, first order, Higuchi and Korsmeyer-Peppas models. The A-BNNs had an average size of 157.0 ± 3.58 nm and A-BLNs had an average size of 173 ± 1.24 nm. The A-BNNs had an average zeta potential of -29.0 ± 1.11 mV and A-BLNs had an average zeta potential of -46.5 ± 1.11 mV. The A-BNNs have an average entrapment efficiency of 94 ± 0.4% and A-BLNs have an average entrapment efficiency of 98 ± 0.14%. The BNNs have an average drug release of 78.12 ± 1.57% and A-BLNs have an average release of 98.41 ± 1.87% over 24 hours. Our results show that the vesicular size dependence influences the resulting nanoparticle drug carrier properties. This is a robust demonstration of the phenomena at the nanoscale that the precursor vesicular system size dependency will be reflected in bulk-engineered nanoparticle properties. These novel nanoparticles are potential candidates for development as an injection to suppress clots in stroke and myocardial infarction., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

Tumor heterogeneity poses a significant challenge in cancer therapy. To address this, we analyze pharmacotherapeutic challenges by categorizing them into static and dynamic barriers, reframing these challenges to improve drug delivery, efficacy, and the development of controlled-release nanomedicines (CRNMs). This pathophysiology-driven approach facilitates the design of novel therapeutics tailored to overcome obstacles in pancreatic ductal adenocarcinoma (PDAC) using nanotechnology. Advanced biomaterials in nanodrug delivery systems offer innovative solutions by combining controlled release, stimuli sensitivity, and smart design strategies. CRNMs are engineered to modulate spatiotemporal signaling and control drug release in PDAC, where resistance to conventional therapies is particularly high. This review explores pharmacokinetic considerations for nanomedicine design, RNA interference (RNAi) for stromal modulation, and the development of targeted nanomedicine strategies. Additionally, we highlight the limitations of current animal models in capturing the complexities of PDAC and discuss notable clinical failures, such as PEGylated hyaluronidase (Phase III HALO 109-301 trial) and evofosfamide (TH-302) with gemcitabine (MAESTRO trial), underscoring the need for improved models and treatment strategies. By targeting pathways like Notch and Hedgehog and incorporating stimuli-sensitive and pathway-modulating agents, CRNMs offer a promising avenue to enhance drug penetration and efficacy, reshaping the paradigm of pancreatic cancer treatment.

Drug solubility is a determining factor for controlled release, and solubility-dependent release kinetics can be modified by changing the drug's state in the polymer matrix through partial molecular imprinting (PMI), although research in this area remains limited. This novel PMI approach creates nanocavities within the polymer by partially retaining the imprinting molecule and trapping the drug. Such a method holds promise for developing advanced biomaterial-based drug delivery systems for anticancer therapies. In this study, we developed microspheres designed for anticancer drug delivery utilizing PMI to enhance controlled release properties. Poly(vinyl alcohol) (PVA) microspheres were partially imprinted with aspirin (ASP) to create nanocavities for gemcitabine (GEM) molecules, inducing a polymorphic shift of GEM within the polymer matrix. This novel PMI approach enhanced drug release properties by enabling control over the drug crystallinity and release rate. The PVA-ASP-GEM complex showed zero-order release kinetics, releasing 21.6% of GEM over 48 h, maintaining steady state release profile. In contrast, nonimprinted PVA-GEM microspheres exhibited first-order kinetics with a faster release of 46.85% in the same period. Quantum insights from density functional theory (DFT) calculations revealed the superior stability of the PVA-ASP-GEM complex, with a binding free energy of -56.03 kcal/mol, compared to -29.07 kcal/mol for PVA-GEM. Molecular dynamics (MD) simulations demonstrated that ASP's presence created nanocavities that restricted GEM's movement, further contributing to the controlled release. Experimental validation through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Raman spectroscopy confirmed the polymorphic transitions within the PVA-ASP-GEM complex. This PMI-based approach offers a promising method for modulating drug release kinetics and improving the stability of anticancer therapeutics, paving the way for innovative biomaterial-based drug delivery systems.

Pelvic exenteration is a surgery done to achieve margin negative resection in locally advanced rectal cancer infiltrating pelvic organs anterior to it. A retrospective observational study of patients undergoing pelvic exenteration for locally advanced rectal cancer was done at a single surgical unit of a tertiary care cancer centre. The period of study was from 1st January 2019 to 30th June 2021. A total of twelve patients underwent pelvic exenteration for locally advanced rectal cancer during the study period. The median duration of surgery was 310 min (range 250 to 380 min). The median duration of hospital stay was 14 days (range 12 to 30 days). Seven patients had documented postoperative complications, either major or minor, with a complication rate of 58.3%. Three patients required re-admission for complications. Two patients had COVID19 infection in the postoperative period but had uneventful recovery. Margin negative resection (R0) was achieved in eight patients (66.67%). Pelvic exenteration for locally advanced rectal cancer is a definitive surgery associated with a high morbidity rate., Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01529-3., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022.)

In this study, we aimed to compare the surgical volume and outcomes between this COVID-19 period and data from non-COVID-19 period of last year. A retrospective observational study was done in one single surgical unit of a dedicated oncology center in a peripheral location in India. The comparison was done between patients undergoing major cancer surgery during the COVID-19 pandemic period of 1st April to 30th June 2020, when a nation-wide lockdown was in force, to a comparable period of last year. Statistical analysis was done using SPSS software 20.0. A total of 72 patients underwent major cancer surgery during this period, with surgery for breast cancer ( n  = 26) being the major sub-site operated. This was a significant decrease from the total 209 major cancer surgeries performed during a similar period of last year (2019) ( p  < 0.05). There were several reasons for the decrease in surgical numbers, including the difficulty in travel and accommodation during the lockdown period. The mean distance of patient's residence from the treating hospital was 45.7 km (range 4 to 165 km). Public transport was in a limbo and inter-state travel was restrictive with mandatory quarantine rules in effect. Morbidity associated with major surgeries was observed to be significantly less during the COVID-19 period compared to the pre-COVID-19 times (8.3% vs 17.2% with a p value of < 0.05), which can probably be attributed to the lesser number of complex surgical procedures being performed. There was no significant difference between the total mortality percentages (2.8% vs 3.8%). A total of 156 PPE kits were used (3-4/per patient) throughout the in-hospital care of the surgical patients included in this study. In the midst of a pandemic, the delivery of surgical cancer care is an essential service and although the surgical volume is significantly hampered due to various reasons, the outcomes are largely unaffected., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Surgical Oncology 2021.)

Background and Aim: Postoperative pancreatic fistula (POPF) is an important cause of major morbidity and mortality after pancreaticoduodenectomy. We intend to estimate the incidence and study the risk factors and outcomes of patients who developed this dreaded complication., Methods: This is a retrospective observational study. We included all patients who underwent pancreaticoduodenectomy at a specialized surgical unit of a single tertiary care cancer center in Northeast India. The period of study was from 23 April 2012 to 27 December 2019. The 2016 update on the definition of POPF by the International Study Group for Pancreatic Fistula was used to define the complication. Chi-square test and Fischer's exact test were applied to categorical variables. t -test was used to quantify mean difference among continuous variables. P value <0.05 was considered statistically significant at 95% confidence interval., Results: A total of 59 patients underwent pancreaticoduodenectomy during the study period with almost equal distribution among males and females (29 and 30 patients respectively). The mean age of the patients was 54.0 years (range 20-72). Grade A, B, and C pancreatic fistulas were seen in five (8.5%), three (5.1%), and two (3.4%) patients, respectively. Preoperative hyperbilirubinemia, pancreatic duct size ≤3 mm, hypoalbuminemia, preoperative biliary decompression, and prolonged duration of surgery were identified as risk factors for POPF. POPF also resulted in increased 90-day mortality (20%)., Conclusion: POPF remains a potentially life-threatening complication of pancreaticoduodenectomies. The knowledge and management of modifiable risk factors for this condition may help in mitigating this problem., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This work attempts to resolve one of the key issues related to the design and development of sustained-release spherule of aspirin for oral formulations, tailored to treat COVID-19. For that, in the Design of Experiments (DOE) an arbitrary interface, "coating efficiency" (CE) is introduced and scaled the cumulative percentage coating (CPC) to get predictable control over drug release (DR). Subsequently, the granules containing ASP are converted to spherules and then to Ethyl cellulose (EC) Coated spherules (CS) by a novel bed coating during the rolling (BCDR) process. Among spherules, one with 0.35 mm than 0.71 mm shows required properties. The CS has a low 120 0 angle by Optical Microscopy (OM), smooth surface without cracks by scanning electron microscopy (SEM), and better flow properties (Angle of repose 29.69 ± 0.78 0 , Carr's index 6.73 ± 2.24%, Hausner's Ratio 1.07 ± 0.03) than granules and spherules. Once certain structure-dependent control over release is attained (EC coated spherules shows 10% reduction in burst release (BR) than uncoated spherules showing a release of 80-91%) the predictability is achieved and Design of space (DOS) by DOE (CE-70.14%and CPC-200% and DR-61.54%) is established. The results of DOE to experimentally validated results were within 20% deviation. The aspirin is changing its crystal structure by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) from Form-I to Form-II showing polymorphism inside the drug reservoir with respect to the process. This CE and CPC approach in DOE can be used for delivery system design of other labile drugs similar to aspirin in emergency situations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The wound healing process involves three continuous stages. Where, any imbalance can lead to the formation of unwanted keloids, hypertrophic scar, or tumors. Keloids are any unpleasant, non-compliant comorbidity affecting a major section of people around the globe who acquire it either genetically or by pathological means as a result of a skin injury. Angiogenesis is unavoidable in the healing process after an injury or disruption of skin to promote tissue regeneration. Uncontrolled angiogenesis during the healing process can initiate the unwanted response in the wound that facilitate keloid. Angiogenic therapy is adapted to accelerate healing after an injury. Else ways, there exists a risk of keloid formation due to excessive angiogenesis during the wound healing process. There are numerous strategies to treat keloid. Anti-angiogenic factors are provided to patients post-surgery to prevent the keloid formation; however, they come into the picture after the formation of keloid. The available strategies to treat keloids are steroidal injections, surgical excision of the keloid, radiotherapy, pressure therapy, the use of cryosurgery, and many more. The available treatments are not promising in reducing the recurrent rate of keloids as there are chances of high re-occurrences with similar/larger lesions on the removed keloid site. In this review, we are discussing the importance of controlled angiogenesis with the help of controlled drug delivery strategies enabling the wound healing process without the induction of keloid., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alopecia or hair loss is a benign treatable disorder which, over time, becomes chronic, affecting a significant fraction of the population that affects the patient's self-esteem and quality of life. The existing treatment regimen for alopecia is inadequate for drug delivery directly to hair follicles to result in continuous hair growth. The challenges are due to multiple-dose regimes and patient non-adherence, where it requires motivated clinical attention. Developing a prolonged drug delivery system by exploration of specific pathways to advance the delivery system into nanomedicine would be beneficial for clinical advancement. In this review, factors affecting the progress of the current therapeutic regimen towards controlled release nanomedicine (CRNM's) are analysed for existing clinical unmet needs, current treatment strategy, and research efforts taken in this direction. Correspondingly, changes in anatomy and pathophysiology of hair growth being analyzed in detail to focus the exact scenario of hair growth cycle and supplementation of medication. Besides, the current treatment regimen with various classes of drugs, their different pathways, and dosing limitations are analyzed. Possibilities of research effort for prolonged drug delivery are discussed in detail, including marketed products, clinical trials as well as various patents filed in the direction. Repurposing of multiple therapeutics using the nanotechnology platform, subsequently, results in a strategy to develop nanomedicine to treat alopecia, which could develop into several technologies (CRNM's), fore coming years from now., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is a worldwide issue, with burgeoning rise in prevalence, morbidity and mortality. Targeted drug delivery, a long sort solution in this regard using controlled release (CR) - nanocarriers, is still a challenge. There is an emerging criticism that, the challenges are due to less appreciation for the biological barriers and lack of corresponding newer technologies. Over the years, more understanding about the biological barriers has come with the progress in characterization techniques. Correspondingly, there is a change in opinion about approaches in clinical trial that; focus of the end point need to be shifted towards disease stabilization for these explorative technologies. Currently, there is a requirement to overcome these newly identified challenges to develop newer affordable therapeutics. The ongoing clinical protocol for therapy using CR-nanocarriers is intravenous injection followed by local targeting to cancer site. This is the most accepted protocol and new CR-nanocarriers are being developed to suit this protocol. In this review, recent progress in treatment of PCa using CR-nanocarriers is analyzed with respect to newly identified biological barriers and design challenges. Possibilities of exploring nanoemulsion (NE) platform for targeted drug delivery to PCa are examined. Repurposing of drugs and combination therapy using NE platform targeted to PCa can be explored for design and development of affordable nanomedicine. In 20yrs. from now there expected to be numerous affordable nanomedicine technologies available in market exploring these lines., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood. Delivery systems mimicking basal release profiles are known as open-loop systems and current marketed products are open-loop systems. Future trend in open-loop systems is to reduce the number of injections per week by enhancing duration of action, by modifying the depot properties. The next generation technologies are closed-loop systems that mimic the pulsatile mode of delivery by pancreas. In closed-loop systems insulin will be released in response to plasma glucose. This review focuses on future trend in open-loop systems; by understanding (a) the secretion of insulin from pancreas, (b) the insulin regulation normal and in DM, (c) insulin depots and (d) the recent progress in open-loop depot technology particularly with respect to nanosystems., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release properties in the combined formulations. Our proof concept study shows that, the conversion of curcumin to a metal-organic supramolecular prodrug improved the solubility, stability and release profile of curcumin. The prodrug approach with the micellisation strategy appears to be more appropriate to deliver intact curcumin in the presence of ceramic particles of varying surface reactivity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The shorter, the more dispersible: An iterative, emulsion-based shortening technique has been used to reduce the length of single-walled carbon nanotubes (SWNTs) to the same order of magnitude as their diameter (ca. 1 nm), thus achieving an effectively "zero-dimensional" structure with improved dispersibility and, after hydroxylation, long-term water solubility. Finally, zero-dimensional SWNTs were positively identified using mass spectrometry for the first time., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Potential error sources in nutrient estimation with the FFQ include inaccurate or biased recall and overestimation or underestimation of intake due to too many or too few items on the FFQ, respectively. Here we report the refinement of an FFQ that overestimated nutrient intake and its validation against multiple 24 h recalls., Study Design: Data on 2527 participants in south India (Trivandrum) were available for the original FFQ (OFFQ) that overestimated nutrient intake (132 food items). After excluding participants with implausible energy intake estimates (<2.72 MJ/d (<650 kcal/d), >15.69 MJ/d (>3750 kcal/d)) we ran stepwise regression analyses with selected nutrients as the outcomes and food intake (servings/d) as predictor variables (n 1867). From these results and expert consultation we refined the FFQ (RFFQ), and validated it by comparing intakes obtained with it and the mean of two 24 h recalls among 100 participants., Results: The OFFQ overestimated usual daily nutrient intake before and after exclusions [for energy: 13.39 (sd 5.46) MJ (3201 (sd 1305) kcal) and 10.96 (sd 2.65) MJ (2619 (sd 634) kcal), respectively]. In stepwise analyses, fifty-seven food items explained 90 % of the variance in nutrients; we retained thirteen food items because participants consumed them at least twice monthly and twelve food items that local nutritionists recommended. Mean energy intake estimated from the RFFQ (eighty-two food items) was 7.94 (sd 2.05) MJ (1897 (sd 489) kcal). The de-attenuated correlations between mean 24 h recall and RFFQ intakes ranged from 0.25 (vitamin A) to 0.82 (fat)., Conclusion: We refined an FFQ that overestimated nutrient intake by shortening and redesigning, and validated it by comparisons with 24 h dietary recall data.