Biomimetic Ghost Nanomedicine-Based Optotheranostics for Cancer.

Theranostic medicine combines diagnostics and therapeutics, focusing on solid tumors at minimal doses. Optically activated photosensitizers are significant examples owing to their photophysical and chemical properties. Several optotheranostics have been tested that convert light to imaging signals, therapeutic radicals, and heat. Upon light exposure, conjugated photosensitizers kill tumor cells by producing reactive oxygen species and heat or by releasing cancer antigens. Despite clinical trials, these molecularly conjugated photosensitizers require protection from their surroundings and a localized direction for site-specific delivery during blood circulation. Therefore, cell membrane biomimetic ghosts have been proposed for precise and safe delivery of these optically active large molecules, which are clinically relevant because of their biocompatibility, long circulation time, bypass of immune cell recognition, and targeting ability. This review focuses on the role of biomimetic nanoparticles in the treatment and diagnosis of tumors through light-mediated diagnostics and therapy, providing insights into their preclinical and clinical status.

Special Issue "Latest Advances in Nanomedicine Strategies for Different Diseases".

We launched this Special Issue amidst the COVID-19 pandemic, spurred by the growing interest in nanotherapeutic formulations for delivering SARS-CoV-2 viral messenger Ribonucleic Acid (mRNA) vaccines [...].

SNAC for Enhanced Oral Bioavailability: An Updated Review.

The delivery of proteins and peptides via an oral route poses numerous challenges to improve the oral bioavailability and patient compliance. To overcome these challenges, as well as to improve the permeation of proteins and peptides via intestinal mucosa, several chemicals have been studied such as surfactants, fatty acids, bile salts, pH modifiers, and chelating agents, amongst these medium chain fatty acid like C10 (sodium caprate) and Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) and its derivatives that have been well studied from a clinical perspective. This current review enumerates the challenges involved in protein and peptide delivery via the oral route, i.e., non-invasive routes of protein and peptide administration. This review also covers the chemistry behind SNAC and toxicity as well as mechanisms to enhance the oral delivery of clinically proven molecules like simaglutide and other small molecules under clinical development, as well as other permeation enhancers for efficient delivery of proteins and peptides.

A Comprehensive Review of mRNA Vaccines.

mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery.

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.

Comparison of cationic liposome and PAMAM dendrimer for delivery of anti-Plk1 siRNA in breast cancer treatment.

Delivery of negatively charged, high molecular weight and unstable siRNA is difficult. The present study describes the development and comparison of cationic liposomes (CLs) and polyamidoamine (PAMAM) dendrimer generation 4 (PG4) nanocarriers of gene for cancer therapy. CLs and PG4 were complexed with anticancer siRNA (siPlk1) to form siPlk1-CLs lipoplex and siPlk1-PG4 dendriplex. siPlk1-CLs/PG4 complexes were characterized for average particle size, zeta potential, fluorescence and integrity of siPlk1 by agarose gel electrophoresis, ethidium bromide intercalation assay, circular dichroism, protection against RNase and stability in serum. The complexation of CLs/siPlk1 and PG4/siPlk1 were at a 100/1 and 2/1 charge ratio respectively. The CLs and PG4 were effective in protecting siPlk1 from RNase activity, also they enhanced the siPlk1 serum stability. Additionally, siPlk1-CLs and siPlk1-PG4 were evaluated by cell culture studies. In vitro anticancer activity study using MCF-7 cells showed that siPlk1-CLs and siPlk1-PG4 causes nearly similar cell death. Both siPlk1-CLs and siPlk1-PG4 resulted in enhanced cellular uptake of siPlk1 in MDA-MB-231 cells compared to naked siPlk1 solution. Cell cycle analysis suggested that increased cell population arrest in subG1 phase by siPlk1-CLs and siPlk1-PG4 compared to naked siPlk1 solution. These observations suggested that CLs and PG4 can be a potential carrier for siPlk1 delivery in breast cancer treatment.

Dithranol-loaded nanostructured lipid carrier-based gel ameliorate psoriasis in imiquimod-induced mice psoriatic plaque model.

OBJECTIVE: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation. SIGNIFICANCE: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis. METHODS: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol). RESULTS: NLCs were prepared with particle size below 300 nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ∼100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control. CONCLUSIONS: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product.

Preparation and Comparison of Oral Bioavailability for Different Nano-formulations of Olaparib.

Olaparib (OLA) is a poly ADP ribose polymerase (PARP) inhibitor approved for germline BRCA-mutated (gBRCAm) advanced ovarian cancer and breast cancer. Low oral bioavailability of this drug requires increase in the dose and frequency causing haematological toxicity in the patients. The purpose of this study is to prepare different nano-formulations of OLA lipospheres (LP) by melt dispersion and nano-suspensions (NSP) by solvent evaporation (SE) and wet milling (WM) techniques and compare oral bioavailability of these formulations. Size of the nano-formulations OLA-LP, OLA-NSPSE and OLA-NSPWM were found to be 126.71 ± 4.54, 128.6 ± 2.34 and 531.1 ± 5.34 nm with polydispersity index below 0.3. In vitro release studies were performed by dialysis bag method where the sustained drug release was observed from nano-formulations until 9 h with Higuchi for OLA suspended in 2.5% w/v sodium carboxy methyl cellulose (OLA-SP), OLA-LP and OLA-NSPWM and Peppas for OLA-NSPSE-based drug release kinetics. In vivo pharmacokinetic studies, haematological toxicity and distribution studies were performed on rats. Results showed that there was an improvement in Cmax, AUCtotal, t1/2 and MRT by OLA nano-formulations when compared with OLA-SP. OLA-SP has shown reduction in WBC, platelets and lymphocytes at 12 and 36 h time points; however, no reduction in cell count was observed with OLA nano-formulations. Distribution studies proved FITC nano-formulations were most rapidly absorbed and distributed when compared with FITC-loaded suspension. From the above results, it was concluded that OLA nano-formulations can be an alternative to enhance the oral bioavailability and to reduce the haematological toxicity of OLA.

Exploring the Potential of Nanotherapeutics in Targeting Tumor Microenvironment for Cancer Therapy.

Advanced research in the field of cancer biology clearly demonstrated the key role of tumor microenvironment (TME) in cancer development and metastasis particularly in solid tumors. Components of TME, being non-neoplastic in nature provide supportive and permissive conditions for the growth of cancer cells. Hence it is important to modify TME in cancer therapy and this would be achieved by better understanding of TME morphological features and functioning of stromal components. Nanotechnology based drug delivery offers various advantages such as prolonged circulation time, delivery of cargo at desired site, improved bioavailability, reduced toxicity etc. over conventional chemotherapeutics. Abnormal characteristic features of TME play a paradoxical role in nanoparticulate drug delivery. Leaky vasculature, acidic and hypoxic conditions of TME helps in the accumulation of tailored nanoparticles whereas high interstitial pressure and dense stroma restrict the extravasation, homogenous distribution of nanocarriers in TME. This review mainly discusses the potential of nanotherapeutics in targeting TME by briefly discussing stromal components, therapeutic opportunities and barriers offered by TME for nanoparticulate drug delivery. Updated information on TME remodeling strategies for improved drug delivery and specific targeting of individual stromal components are also outlined.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

Peptide Conjugated Boron Neutron Capture Therapy for Enhanced Tumor Targeting.

A cutting-edge non-invasive cancer treatment method called boron neutron capture therapy (BNCT) allows for the removal of cancerous tumor cells with the least possible damage to healthy tissue. It involves the exposure of cancer cells with low-energy thermal neutrons, boron-10 (10B) cellular uptake causes cancer cell death by producing alpha particles and recoiling lithium-7 (7 Li) nuclei. Despite positive outcomes from clinical trials conducted all around the world, these substances have relatively limited tumor selectivity or low boron content per molecule. The development of new boron delivery agents with more selectivity and enhanced boron loading would advance this technique and promote its use in clinics as a primary cancer treatment. As peptide-binding cell surface receptors are typically overexpressed on cancer cells, they can be seen as interesting targets for targeted tumor therapy. The attachment of meta-carboranes to peptide conjugates that target tumor cells specifically by their overexpressed receptors may be a method to get around these problems. A state-of-the-art overview of current developments in the application of BNCT for cancer targeted therapy via peptide conjugation is the goal of this review.

Genome editing and its role in vaccine, diagnosis, and therapeutic advancement.

Genome editing involves precise modification of specific nucleotides in the genome using nucleases like CRISPR/Cas, ZFN, or TALEN, leading to increased efficiency of homologous recombination (HR) for gene editing, and it can result in gene disruption events via non-homologous end joining (NHEJ) or homology-driven repair (HDR). Genome editing, particularly CRISPR-Cas9, revolutionizes vaccine development by enabling precise modifications of pathogen genomes, leading to enhanced vaccine efficacy and safety. It allows for tailored antigen optimization, improved vector design, and deeper insights into host genes' impact on vaccine responses, ultimately enhancing vaccine development and manufacturing processes. This review highlights different types of genome editing methods, their associated risks, approaches to overcome the shortcomings, and the diverse roles of genome editing.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

BACKGROUND: Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. HYPOTHESIS: Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. CONCLUSION: The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Collagen-Based Hydrogels for the Eye: A Comprehensive Review.

Collagen-based hydrogels have emerged as a highly promising platform for diverse applications in ophthalmology, spanning from drug delivery systems to biomedical interventions. This review explores the diverse sources of collagen, which give rise to different types of collagen protein. The critical isolation and purification steps are discussed, emphasizing their pivotal role in preparing collagen for biomedical use. To ensure collagen quality and purity, and the suitability of collagen for targeted applications, a comprehensive characterization and quality control are essential, encompassing assessments of its physical, chemical, and biological properties. Also, various cross-linking collagen methods have been examined for providing insight into this crucial process. This comprehensive review delves into every facet of collagen and explores the wide-ranging applications of collagen-based hydrogels, with a particular emphasis on their use in drug delivery systems and their potential in diverse biomedical interventions. By consolidating current knowledge and advancements in the field, this review aims to provide a detailed overview of the utilization of engineered collagen-based hydrogels in ocular therapeutics.

Engineered Liposomes in Interventional Theranostics of Solid Tumors.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

Versatility of Liposomes for Antisense Oligonucleotide Delivery: A Special Focus on Various Therapeutic Areas.

Nucleic acid therapeutics, specifically antisense oligonucleotides (ASOs), can effectively modulate gene expression and protein function, leading to long-lasting curative effects. The hydrophilic nature and large size of oligonucleotides present translational challenges, which have led to the exploration of various chemical modifications and delivery systems. The present review provides insights into the potential role of liposomes as a drug delivery system for ASOs. The potential benefits of liposomes as an ASO carrier, along with their method of preparation, characterization, routes of administration, and stability aspects, have been thoroughly discussed. A novel perspective in terms of therapeutic applications of liposomal ASO delivery in several diseases such as cancer, respiratory disease, ophthalmic delivery, infectious diseases, gastrointestinal disease, neuronal disorders, hematological malignancies, myotonic dystrophy, and neuronal disorders remains the major highlights of this review.

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core selection, approaches for coating nanoparticle cores with the cell membrane, and characterization methods. Moreover, this review underscores strategies employed to enhance the multi-functionality of these nanosystems, including lipid insertion, membrane hybridization, metabolic engineering, and genetic modification. Additionally, the applications of these bioinspired nanosystems in cancer diagnosis and therapeutics are discussed, along with the recent advances in this field. Through a comprehensive exploration of membrane-coated nanosystems, this review provides valuable insights into their potential for precise cancer theranostics.

Emerging Trends in Lipid-Based Vaccine Delivery: A Special Focus on Developmental Strategies, Fabrication Methods, and Applications.

Lipid-based vaccine delivery systems such as the conventional liposomes, virosomes, bilosomes, vesosomes, pH-fusogenic liposomes, transferosomes, immuno-liposomes, ethosomes, and lipid nanoparticles have gained a remarkable interest in vaccine delivery due to their ability to render antigens in vesicular structures, that in turn prevents its enzymatic degradation in vivo. The particulate form of lipid-based nanocarriers confers immunostimulatory potential, making them ideal antigen carriers. Facilitation in the uptake of antigen-loaded nanocarriers, by the antigen-presenting cells and its subsequent presentation through the major histocompatibility complex molecules, leads to the activation of a cascade of immune responses. Further, such nanocarriers can be tailored to achieve the desired characteristics such as charge, size, size distribution, entrapment, and site-specificity through modifications in the composition of lipids and the selection of the appropriate method of preparation. This ultimately adds to its versatility as an effective vaccine delivery carrier. The current review focuses on the various lipid-based carriers that have been investigated to date as potential vaccine delivery systems, the factors that affect their efficacy, and their various methods of preparation. The emerging trends in lipid-based mRNA vaccines and lipid-based DNA vaccines have also been summarized.

HPMCAS-Based Amorphous Solid Dispersions in Clinic: A Review on Manufacturing Techniques (Hot Melt Extrusion and Spray Drying), Marketed Products and Patents.

Today, therapeutic candidates with low solubility have become increasingly common in pharmaceutical research pipelines. Several techniques such as hot melt extrusion, spray drying, supercritical fluid technology, electrospinning, KinetiSol, etc., have been devised to improve either or both the solubility and dissolution to enhance the bioavailability of these active substances belonging to BCS Class II and IV. The principle involved in all these preparation techniques is similar, where the crystal lattice of the drug is disrupted by either the application of heat or dissolving it in a solvent and the movement of the fine drug particles is arrested with the help of a polymer by either cooling or drying to remove the solvent. The dispersed drug particles in the polymer matrix have higher entropy and enthalpy and, thereby, higher free energy in comparison to the crystalline drug. Povidone, polymethaacrylate derivatives, hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate derivatives are commonly used as polymers in the preparation of ASDs. Specifically, hydroxypropylmethylcellulose acetate succinate (HPMCAS)-based ASDs have become well established in commercially available products and are widely explored to improve the solubility of poorly soluble drugs. This article provides an analysis of two widely used manufacturing techniques for HPMCAS ASDs, namely, hot melt extrusion and spray drying. Additionally, details of HPMCAS-based ASD marketed products and patents have been discussed to emphasize the commercial aspect.

Peptide Engraftment on PEGylated Nanoliposomes for Bone Specific Delivery of PTH (1-34) in Osteoporosis.

Bone-specific functionalization strategies on liposomes are promising approaches to delivering the drug in osteoporotic conditions. This approach delivers the drug to the bone surface specifically, reduces the dose and off-target effects of the drug, and thereby reduces the toxicity of the drug. The purpose of the current research work was to fabricate the bone-specific peptide conjugated pegylated nanoliposomes to deliver anabolic drug and its physicochemical evaluations. For this, a bone-specific peptide (SDSSD) was synthesized, and the synthesized peptide was conjugated with a linker (DSPE-PEG2000-COOH) to obtain a bone-specific conjugate (SDSSD-DSPE). Purified SDSSD-DSPE was characterized by HPLC, Maldi-TOF, NMR, and Scanning Electron Microscope/Energy Dispersive Spectroscopy (SEM/EDS). Further, peptide-conjugated and anabolic drug-encapsulated liposomes (SDSSD-LPs) were developed using the ethanol injection method and optimized by Central Composite Design (CCD) using a statistical approach. Optimized SDSSD-LPs were evaluated for their physicochemical properties, including surface morphology, particle size, zeta potential, in vitro drug release, and bone mineral binding potential. The obtained results from these studies demonstrated that SDSSD-DSPE conjugate and SDSSD-LPs were optimized successfully. The particle size, % EE, and zeta potential of SDSSD-LPs were observed to be 183.07 ± 0.85 nm, 66.72 ± 4.22%, and -25.03 ± 0.21 mV, respectively. SDSSD-LPs demonstrated a sustained drug release profile. Further, the in vitro bone mineral binding assay demonstrated that SDSSD-LPs deliver the drug to the bone surface specifically. These results suggested that SDSSD-LPs could be a potential targeting approach to deliver the anabolic drug in osteoporotic conditions.