Drug Nanoformulations Research Articles

Hyaluronic acid act as drug self-assembly chaperone and co-assembled with celalstrol for ameliorating non-alcoholic steatohepatitis

Nanoformulations of therapeutic drugs with diverse chemical structures are often complex to produce and lack a universal synthesis approach. Herein, we demonstrate that hyaluronic acid (HA) can function as an assembly chaperone, facilitating the formulation of various chemical compounds into nanoparticles without necessitating chemical modification. As a proof of concept, celastrol-HA co-assembled nanoparticles (CHNPs) were synthesized and utilized in the multifactorial treatment of non-alcoholic steatohepatitis (NASH). By simply blending an aqueous solution of HA and celastrol, we achieved the formation of homogeneous, stable, and biocompatible nanoparticles, effectively addressing the critical issues associated with celastrol's poor water solubility and high systemic toxicity. of celastrol. Ex vivo and in vivo experiments demonstrated that CHNPs ameliorated NASH by inhibiting macrophage M1 polarization, reducing liver inflammation and lipid deposition, and improving metabolic disorders. Furthermore, CHNPs reduced systemic toxicity and enhanced the bioavailability of celastrol. The simplicity of the HA-based nanoparticles may facilitate the development of translational nanomedicines.

Nano-formulations for the Management of Epilepsy: Synthetic and Herbal Drug Perspectives

Introduction: Epilepsy is a multifaceted neurological disorder impacting many individuals globally. Although the main treatment method is through medicines, many patients do not respond to existing drugs. This has spurred extensive research for new therapeutic targets and drug delivery methods. Inflammation and oxidative stress have been associated with the development and progression of epilepsy. Nanomedicine-based treatments focussing on these pathways could provide a promising way to enhance treatment results. Objective: This review aims to provide insights into enhancing antiepileptic therapy through the development of nanoformulations of synthetic and herbal drugs. Methods: A comprehensive review of existing literature was conducted to evaluate the potential of nanoformulations in improving the delivery and efficacy of antiepileptic drugs. The review covers the pathophysiological hypotheses of epilepsy, including the glutamatergic, GABAergic, oxidative stress, and neuroinflammation hypotheses, and examines the role of neurotransmitter imbalances in seizure activity. Results: Nanoformulations offer promising advantages for epilepsy treatment by enhancing drug delivery across the blood-brain barrier, reducing required dosages, and minimizing side effects. The utilization of nanoparticles can improve the bioavailability and targeting of AEDs, potentially leading to better seizure control. However, challenges such as ensuring biocompatibility and optimizing nanoparticle characteristics remain. Conclusion: While significant progress has been made in understanding epilepsy and developing treatments, the disorder continues to pose challenges. Nanoformulations represent a promising area of research that could lead to more effective and targeted therapies for epilepsy, although further studies are needed to address the associated challenges and fully realize their potential.

Development of erythromycin loaded PLGA nanoparticles for improved drug efficacy and sustained release against bacterial infections and biofilm formation

Bacterial infections are a common cause of sepsis, often leading to high patient mortality. Such infections are challenging to treat due to bacterial resistance to many existing drugs. Erythromycin (Ery) is a macrolide antibiotic used against bacterial infections with reported resistance. Recently, synthetic poly-lactide co-glycolic acid (PLGA) polymer nanoparticles (NPs) have displayed improved drug delivery characteristics and biocompatibility. In this study, PLGA-Ery NPs were synthesized by the o/w emulsion diffusion method, having a particle size of 159 ± 23 nm and displayed 71.89 % of encapsulation efficiency. The PLGA-Ery NPs showed 1.5, 2.1 and 1.5-fold improved MIC and antibacterial efficacy against E. coli, S. aureus, and P. aeruginosa, respectively than the pure drug. As illustrated by scanning electron microscopy, PLGA-Ery NPs caused damage to the bacterial cell walls. Furthermore, a surface coating with PLGA-Ery NPs on a glass surface showed efficient inhibition (>90 %) of the biofilm formation by P. aeruginosa, as determined by fluorescence microscopy and MTT assay. This study demonstrates that PLGA-Ery NPs can increase the efficiency of erythromycin and can suppress the growth and biofilm formation of P. aeruginosa. Such polymeric nanoparticles drug nanoformulations have potential as an antimicrobial and as a surface coating for medical devices.

Glochidion Species: A Review on Phytochemistry and Pharmacology

Objectives The genus Glochidion (the family Phyllanthaceae) is used for various medicinal purposes, such as dysentery, diarrhea, cough, and skin protection. A review of phytochemical and pharmacological aspects for this remains unavailable. The current study tends to sum up a detailed list of phytochemicals, and their role in biological examinations. Methods References in English were obtained by an extensive search across various electronic data sources, encompassing Web of Science, PubMed, Google Scholar, and Science Direct. The “Sci-Finder” was also utilized to find references and revise chemical structures. Referenced documents have been gathered from the 1960s to date. It also noted that Glochidion, phytochemistry, and pharmacology are likely the keywords to seek for references. Results Over 240 naturally occurring phytochemicals were isolated and identified from various Glochidion tissues, including terpenoids, sterols, saponins, lignans, flavonoids, mono-phenols, megastigmanes, butenolides, glycosides, alkaloids, cyanogens, tocopherols, fatty acids, and others. Three naturally occurring triterpenoids glochidonol, glochidiol, and glochidone are the likely characteristic metabolites, being isolated frequently. Glochidion crude extracts and their isolated compounds have been demonstrated as potential agents in various pharmacological targets, such as cytotoxicity, antioxidant, antiinflammation, and neuron and liver protection. Conclusion Several isolates acted as promising agents in pharmacological assays. The anticancer mechanisms of various triterpenoids and saponins, especially new and potential compounds, are expected. Pharmacological advancements to enhance the efficacies of Glochidion constituents, such as synergistic combinations and nano-drug formulations, are encouraged.

Self‐Nanoformulating Poly(2‐oxazoline) and Poly(2‐oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

AbstractA pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer.

An Insight into Cubosomal Drug Delivery Approaches: An Explicative Review.

Cubosomes, a novel drug delivery system, have gained significant attention in recent years due to their unique self-assembled structures and enhanced drug encapsulation capabilities. They are administered by oral, ophthalmic, transdermal, and chemotherapeutic routes, to name a few. Due to their many potential benefits-which include high drug dispersal due to the cubic structure, a large surface area, a relatively simple manufacturing process, biodegradability, the capacity to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and the biodegradability of lipids-cubosomes show enormous promise in drug nanoformulations for cancer therapeutics. The most common preparation method involves emulsifying a monoglyceride with a polymer, homogenizing, and then sonicating the mixture. Two distinct approaches to preparing are top-down and bottom-up. This evaluation will examine the materials, methods of preparation, cubosome-related drug encapsulating techniques, drug loading, release mechanism, and their uses. The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents (2015-2024), the keywords "cubosome; drug delivery systems, nano-carrier, theranostic, drug release mechanism" and others of a similar nature were utilized. This review will conduct a comprehensive analysis of the cubosome-related composition, production methods, drug encapsulating strategies, drug release mechanisms, and applications. Moreover, the difficulties encountered in fine-tuning different parameters to improve loading capabilities and prospects are also discussed. Innovation in pharmaceutical research and development can be stimulated by the knowledge gathered about cubosomal drug delivery methods. Through the clarification of the mechanisms involved in drug release from cubosomes and the investigation of innovative fabrication procedures, scientists can enhance the cubosomal formulation design for targeted therapeutic uses. </p>.

Revealing molecular dynamics of nanoparticles' antimicrobial activity, toxicities and coping up strategies

There is a growing interest in nanoformulations of medicinal drugs for antibacterial, antiviral, antifungal, antiprastic, and antioxidant drug delivery applications by researchers. Using nanoformulations, the conventional medicines have enhanced their functional properties and are more targeted to specific distribution sites. Some Nanoformulations gaining prominence in the pharmaceutical industry are hydrogels, nanocrystals, polymeric nanoparticles, liposomes, nanoemulsions, and micelles. The metal nanoparticles (silver, gold, iron oxide, and others) and nanoemulsions cause protein and DNA damage, producinge ROS (reactive oxygen species) as salient antimicrobial tools. Nanomaterials have been utilized in biomedical applications, spanning metals, nonmetallic/inorganic materials, and biodegradable materials. Human cells exhibit toxicity (e.g.Titanium dioxide) towards nanoparticles (NPs) due to the presence of synthetic chemicals as surface functional agents. Consequently, the nanoparticles alone can induce hepatotoxicity, skin sensitization, and damage. A focus on strategies such as coupling agents has been used in recent advancements aimed at reducing the toxicity of nanoformulations. These modified nanostructures provide safer and more efficient biomedical applications by reducing toxicity and enhancing antimicrobial activity.

Unveiling the Spatiotemporal and Dose Responses within a Single Live Cancer Cell to Photoswitchable Upconversion Nanoparticle Therapeutics Using Hybrid Hyperspectral Stimulated Raman Scattering and Transient Absorption Microscopy.

Photodynamic therapy (PDT) provides an alternative approach to targeted cancer treatment, but the therapeutic mechanism of advanced nanodrugs applied to live cells and tissue is still not well understood. Herein, we employ the hybrid hyperspectral stimulated Raman scattering (SRS) and transient absorption (TA) microscopy developed for real-time in vivo visualization of the dynamic interplay between the unique photoswichable lanthanide-doped upconversion nanoparticle-conjugated rose bengal and triphenylphosphonium (LD-UCNP@CS-Rb-TPP) probe synthesized and live cancer cells. The Langmuir pharmacokinetic model associated with SRS/TA imaging is built to quantitatively track the uptakes and pharmacokinetics of LD-UCNP@CS-Rb-TPP within cancer cells. Rapid SRS/TA imaging quantifies the endocytic internalization rates of the LD-UCNP@CS-Rb-TPP probe in individual HeLa cells, and the translocation of LD-UCNP@CS-Rb-TPP from mitochondria to cell nuclei monitored during PDT can be associated with mitochondria fragmentations and the increased nuclear membrane permeability, cascading the dual organelle ablations in cancer cells. The real-time SRS spectral changes of cellular components (e.g., proteins, lipids, and DNA) observed reflect the PDT-induced oxidative damage and the dose-dependent death pattern within a single live cancer cell, thereby facilitating the real-time screening of optimal light dose and illumination duration controls in PDT. This study provides new insights into the further understanding of drug delivery and therapeutic mechanisms of photoswitchable LD-UCNP nanomedicine in live cancer cells, which are critical in the optimization of nanodrug formulations and development of precision cancer treatment in PDT.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Impact of a Polymer-Based Nanoparticle with Formoterol Drug as Nanocarrier System In Vitro and in an Experimental Asthmatic Model.

The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings.

Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery.

Synthetic polypeptides are biocompatible and biodegradable macromolecules whose composition and architecture can vary over a wide range. Their unique ability to form secondary structures, as well as different pathways of modification and biofunctionalization due to the diversity of amino acids, provide variation in the physicochemical and biological properties of polypeptide-containing materials. In this review article, we summarize the advances in the synthesis of polypeptides and their copolymers and the application of these systems for drug delivery in the form of (nano)particles or hydrogels. The issues, such as the diversity of polypeptide-containing (nano)particle types, the methods for their preparation and drug loading, as well as the influence of physicochemical characteristics on stability, degradability, cellular uptake, cytotoxicity, hemolysis, and immunogenicity of polypeptide-containing nanoparticles and their drug formulations, are comprehensively discussed. Finally, recent advances in the development of certain drug nanoformulations for peptides, proteins, gene delivery, cancer therapy, and antimicrobial and anti-inflammatory systems are summarized.

Emerging Treatment Options of Pluronic in Designing Colloidal Nano and Microcarriers Carriers for Various Therapies.

Poloxamers, commonly known as Pluronics, are a special family of synthetic tri-block copolymers with a core structure made of hydrophobic poly (propylene oxide) chains sandwiched by two hydrophilic poly (ethylene oxide) chains. It is possible to modify the mechanical, bioactive, and microstructural characteristics of Pluronics to simulate the behavior of different types of tissues. Additionally, they are auspicious drug carriers with the capacity to increase therapeutic agent availability and to design nano-drug formulations for various ailments. The nanoformulation composed of Pluronics is more susceptible to cancer cells due to their amphiphilic nature and feature of selfassembling into micelles. Today's expanding poloxamer research is creating new hopes that increase the possibility of new remedies for a brand-new nanomedicine age treatment. This article provides a concise overview of the classification, grading, and attributes of drug delivery systems (DDSs) as well as the potential for Pluronics to create micro and nanocarriers. We subsequently discuss its utility in drug delivery for cancer, gene therapy, anti-infective therapy, antioxidants, anti-diabetic drugs, anti-HIV, Alzheimer's disease, and antimicrobial drugs. This review also highlighted several patented formulations that contain various grades of Pluronics in one or more different ways. The recent findings in fundamental research in the field properly demonstrate the strong interest in these novel pharmaceutical strategies.

Enhancing Ezetimibe Anticancer Activity Through Development of Drug Nano-Micelles Formulations: A Promising Strategy Supported by Molecular Docking.

Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations. Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed. The prepared formulations were in the nano-size range (34.01 ± 2.00-278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC50 against MCF-7 (4.51 µg/mL) and T47D (8.22 µg/mL) cancer cells. When T47D cells were treated with IC50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death. These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer.

A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy

DNA methyltransferase inhibitors (DNMTis) have found widespread application in the management of cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA methyltransferase inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for cancer treatment.

Antibacterial effects of quercetagetin are significantly enhanced upon conjugation with chitosan engineered copper oxide nanoparticles.

The development of antibiotic alternatives that entail distinctive chemistry and modes of action is necessary due to the threat posed by drug resistance. Nanotechnology has gained increasing attention in recent years, as a vehicle to enhance the efficacy of existing antimicrobials. In this study, Chitosan copper oxide nanoparticles (CHI-CuO) were synthesized and were further loaded with Quercetagetin (QTG) to achieve the desired (CHI-CuO-QTG). Size distribution, zeta potential and morphological analysis were accomplished. Next, the developed CHI-CuO-QTG was assessed for synergistic antibacterial properties, as well as cytotoxic attributes. Bactericidal assays revealed that CHI-CuO conjugation showed remarkable effects and enhanced QTG effects against a range of Gram + ve and Gram-ve bacteria. The MIC50 of QTG against S. pyogenes was 107µg/mL while CHI-CuO-QTG reduced it to 9µg/mL. Similar results were observed when tested against S. pneumoniae. Likewise, the MIC50 of QTG against S. enterica was 38µg/mL while CHI-CuO-QTG reduced it to 7µg/mL. For E. coli K1, the MIC50 of QTG was 42µg/mL while with CHI-CuO-QTG it was 23µg/mL. Finally, the MIC50 of QTG against S. marcescens was 98µg/mL while CHI-CuO-QTG reduced it to 10µg/mL. Notably, the CHI-CuO-QTG nano-formulation showed limited damage when tested against human cells using lactate dehydrogenase release assays. Importantly, bacterial-mediated human cell damage was reduced by prior treatment of bacteria using drug nano-formulations. These findings are remarkable and clearly demonstrate that drug-nanoparticle formulations using nanotechnology is an important avenue in developing potential therapeutic interventions against microbial infections.

Nanoparticle-Based Therapies in Hypertension.

Nearly 1.4 billion people worldwide suffer from arterial hypertension, a significant risk factor for cardiovascular disease which is now the leading cause of death. Despite numerous drugs designed to treat hypertension, only ≈14% of hypertensive individuals have their blood pressure under control. A critical factor negatively impacting the efficacy of available treatments is their poor bioavailability. This leads to increased dosing requirements which can result in more side effects, resulting in patient noncompliance. A recent solution to improve dosing and bioavailability issues has been to incorporate drugs into nanoparticle carriers, with over 50 nanodrugs currently on the market across all diseases, and another 51 currently in clinical trials. Given their ability to improve solubility and bioavailability, nanoparticles may offer significant advantages in the formulation of antihypertensives to overcome pharmacokinetic shortcomings. To date, however, no antihypertensive nanoformulations have been clinically approved. This review assesses in vivo study data from preclinical antihypertensive nanoformulation development and testing. Combined, the results of these studies suggest nanoformulation of antihypertensive drugs may be a promising solution to overcome the poor efficacy of currently available antihypertensives, and with further advances has the potential to open paths for new substances that have heretofore been clinically unrealistic due to poor bioavailability.

Macromolecules and nanomaterials loaded with mitomycin C as promising new treatment option Cancer drug nanoformulation: A literature review

Macromolecules and nanomaterials loaded with mitomycin C as promising new treatment option Cancer drug nanoformulation: A literature review

CXCR4 Targeting Nanoplatform for Transcriptional Activation of Latent HIV-1 Infected T Cells.

Antiretroviral drugs are limited in their ability to target latent retroviral reservoirs in CD4+ T cells, highlighting the need for a T cell-targeted drug delivery system that activates the transcription of inactivated viral DNA in infected cells. Histone deacetylase inhibitors (HDACi) disrupt chromatin-mediated silencing of the viral genome and are explored in HIV latency reversal. But single drug formulations of HDACi are insufficient to elicit therapeutic efficacy, warranting combination therapy. Furthermore, protein kinase C activators (PKC) have shown latency reversal activity in HIV by activating the NF-κB signaling pathway. Combining HDACi (SAHA) with PKC (PMA) activators enhances HIV reservoir activation by promoting chromatin decondensation and subsequent transcriptional activation. In this study, we developed a mixed nanomicelle (PD-CR4) drug delivery system for simultaneous targeting of HIV-infected CD4+ T cells with two drugs, suberoylanilide hydroxamic acid (SAHA) and phorbol 12-myristate 13-acetate (PMA). SAHA is a HDACi that promotes chromatin decondensation, while PMA is a PKC agonist that enhances transcriptional activation. The physicochemical properties of the formulated PD-CR4 nanoparticles were characterized by NMR, CMC, DLS, and TEM analyses. Further, we investigated in vitro safety profiles, targeting efficacy, and transcriptional activation of inactivated HIV reservoir cells. Our results suggest that we successfully prepared a targeted PD system with dual drug loading. We have compared latency reversal efficacy of a single drug nanoformulation and combination drug nanoformulation. Final PD-SP-CR4 successfully activated infected CD4+ T cell reservoirs and showed enhanced antigen release from HIV reservoir T cells, compared with the single drug treatment group as expected. To summarize, our data shows PD-SP-CR4 has potential T cell targeting efficiency and efficiently activated dormant CD4+ T cells. Our data indicate that a dual drug-loaded particle has better therapeutic efficacy than a single loaded particle as expected. Hence, PD-CR4 can be further explored for HIV therapeutic drug delivery studies.

Cubosomes in Drug Delivery-A Comprehensive Review on Its Structural Components, Preparation Techniques and Therapeutic Applications.

Cubosomes are lipid vesicles that are comparable to vesicular systems like liposomes. Cubosomes are created with certain amphiphilic lipids in the presence of a suitable stabiliser. Since its discovery and designation, self-assembled cubosomes as active drug delivery vehicles have drawn much attention and interest. Oral, ocular, transdermal, and chemotherapeutic are just a few of the drug delivery methods in which they are used. Cubosomes show tremendous potential in drug nanoformulations for cancer therapeutics because of their prospective advantages, which include high drug dispersal due to the structure of the cubic, large surface area, a relatively simple manufacturing process, biodegradability, ability to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and biodegradability of lipids. The most typical technique of preparation is the simple emulsification of a monoglyceride with a polymer, followed by sonication and homogenisation. Top-down and bottom-up are two different sorts of preparation techniques. This review will critically analyse the composition, preparation techniques, drug encapsulation approaches, drug loading, release mechanism and applications relevant to cubosomes. Furthermore, the challenges faced in optimising various parameters to enhance the loading capacities and future potentialities are also addressed.

Feasibility of Coacervate-Like Nanostructure for Instant Drug Nanoformulation.

Despite the enormous advancements in nanomedicine research, a limited number of nanoformulations are available on the market, and few have been translated to clinics. An easily scalable, sustainable, and cost-effective manufacturing strategy and long-term stability for storage are crucial for successful translation. Here, we report a system and method to instantly formulate NF achieved with a nanoscale polyelectrolyte coacervate-like system, consisting of anionic pseudopeptide poly(l-lysine isophthalamide) derivatives, polyethylenimine, and doxorubicin (Dox) via simple "mix-and-go" addition of precursor solutions in seconds. The coacervate-like nanosystem shows enhanced intracellular delivery of Dox to patient-derived multidrug-resistant (MDR) cells in 3D tumor spheroids. The results demonstrate the feasibility of an instant drug formulation using a coacervate-like nanosystem. We envisage that this technique can be widely utilized in the nanomedicine field to bypass the special requirement of large-scale production and elongated shelf life of nanomaterials.