Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties.

In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste. To date, numerous formulations have been developed for achieving tissue-specific drug targeting and reducing toxic side effects, as well as for improving drug stability. The development of prodrugs represents a promising strategy in targeted cancer therapy for improving the selectivity, efficacy and stability of active compounds. Recent studies show that the incorporation of anticancer drugs into vesicular systems, such as polymeric micelles or cyclodextrins, or the use of nanocarriers containing chemotherapeutics that conjugate to monoclonal antibodies can improve solubility, pharmacokinetics, cellular absorption and stability. In this study, we summarize the latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems.

Insightful exploring of advanced nanocarriers for the topical/transdermal treatment of skin diseases.

Dermatological products constitute a big segment of the pharmaceutical market. From conventional products to more advanced ones, a wide variety of dosage forms have been developed till current date. A representative of the advanced delivery means is carrier-based systems, which can load large number of drugs for treatment of dermatological diseases, or simply for cosmeceutical purposes. To make them more favorable for topical delivery, further incorporation of these carriers in a topical vehicle, such as gels or creams is made. Therefore in this review article, an overview is compiled of the most commonly encountered novel carrier based topical delivery systems; namely lipid based (nanoemulsions, microemulsions, solid lipid nanoparticles [SLNs] and nanostructured lipid carriers [NLCs]), and vesicular carriers (non-deformable, such as liposomes, niosomes, emulsomes and cerosomes, and deformable, such as transfersomes, ethosomes, transethosomes, and penetration enhancer vesicles), with special emphasis on those loaded in a secondary gel vehicle. A special focus was made on the commonly encountered dermatological diseases, such as bacterial and fungal infections, psoriasis, dermatitis, eczema, vitiligo, oxidative damage, aging, alopecia, and skin cancer.

Unlocking the potential of nanocarrier-mediated mRNA delivery across diverse biomedical frontiers: A comprehensive review.

Messenger RNA (mRNA) has gained marvelous attention for managing and preventing various conditions like cancer, Alzheimer's, infectious diseases, etc. Due to the quick development and success of the COVID-19 mRNA-based vaccines, mRNA has recently grown in prominence. A lot of products are in clinical trials and some are already FDA-approved. However, still improvements in line of optimizing stability and delivery, reducing immunogenicity, increasing efficiency, expanding therapeutic applications, scalability and manufacturing, and long-term safety monitoring are needed. The delivery of mRNA via a nanocarrier system gives a synergistic outcome for managing chronic and complicated conditions. The modified nanocarrier-loaded mRNA has excellent potential as a therapeutic strategy. This emerging platform covers a wide range of diseases, recently, several clinical studies are ongoing and numerous publications are coming out every year. Still, many unexplained physical, biological, and technical problems of mRNA for safer human consumption. These complications were addressed with various nanocarrier formulations. This review systematically summarizes the solved problems and applications of nanocarrier-based mRNA delivery. The modified nanocarrier mRNA meaningfully improved mRNA stability and abridged its immunogenicity issues. Furthermore, several strategies were discussed that can be an effective solution in the future for managing complicated diseases.

Beyond Traditional Sunscreens: A Review of Liposomal-Based Systems for Photoprotection.

Sunscreen products are essential for shielding the skin from ultraviolet (UV) radiation, a leading cause of skin cancer. While existing products serve this purpose, there is a growing need to enhance their efficacy while minimizing potential systemic absorption of UV filters and associated toxicological risks. Liposomal-based formulations have emerged as a promising approach to address these challenges and develop advanced photoprotective products. These vesicular systems offer versatility in carrying both hydrophilic and lipophilic UV filters, enabling the creation of broad-spectrum sunscreens. Moreover, their composition based on phospholipids, resembling that of the stratum corneum, facilitates adherence to the skin's surface layers, thereby improving photoprotective efficacy. The research discussed in this review underscores the significant advantages of liposomes in photoprotection, including their ability to limit the systemic absorption of UV filters, enhance formulation stability, and augment photoprotective effects. However, despite these benefits, there remains a notable gap between the potential of liposomal systems and their utilization in sunscreen development. Consequently, this review emphasizes the importance of leveraging liposomes and related vesicular systems as innovative tools for crafting novel and more efficient photoprotective formulations.

Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery.

Ocular drug delivery poses unique challenges due to the complex anatomical and physiological barriers of the eye. Conventional dosage forms often fail to achieve optimal therapeutic outcomes due to poor bioavailability, short retention time, and off-target effects. In recent years, vesicular drug delivery systems have emerged as promising solutions to address these challenges. Vesicular systems, such as liposome, niosome, ethosome, transfersome, and others (bilosome, transethosome, cubosome, proniosome, chitosome, terpesome, phytosome, discome, and spanlastics), offer several advantages for ocular drug delivery. These include improved drug bioavailability, prolonged retention time on the ocular surface, reduced systemic side effects, and protection of drugs from enzymatic degradation and dilution by tears. Moreover, vesicular formulations can be engineered for targeted delivery to specific ocular tissues or cells, enhancing therapeutic efficacy while minimizing off-target effects. They also enable the encapsulation of a wide range of drug molecules, including hydrophilic, hydrophobic, and macromolecular drugs, and the possibility of combination therapy by facilitating the co-delivery of multiple drugs. This review examines vesicular drug delivery systems, their advantages over conventional drug delivery systems, production techniques, and their applications in management of ocular diseases.

A Discursive Review of Recent Development and Patents on Glycerosomes.

BACKGROUND: To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect. OBJECTIVE: The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery. CONCLUSION: Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development.

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer's disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood-brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs.

Recent Developments in Oral Delivery of Vaccines Using Nanocarriers.

As oral administration of vaccines is the preferred route due to its high patient compliance and ability to stimulate both cellular and humoral immune responses, it is also associated with several challenges that include denaturation of vaccine components in the acidic environment of the stomach, degradation from proteolytic enzymes, and poor absorption through the intestinal membrane. To achieve effective delivery of such biomolecules, there is a need to investigate novel strategies of formulation development that can overcome the barriers associated with conventional vaccine delivery systems. Nanoparticles are advanced drug delivery carriers that provide target-oriented delivery by encapsulating vaccine components within them, thus making them stable against unfavorable conditions. This review provides a detailed overview of the different types of nanocarriers and various approaches that can enhance oral vaccine delivery.

Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration.

Drug delivery systems (DDS) based on nanocarriers are designed to transport therapeutic agents to specific areas of the body where they are required to exhibit pharmacodynamic effect. These agents rely on an appropriate carrier to protect them from rapid degradation or clearance and enhance their concentration in target tissues. Spanlastics, an elastic, deformable surfactant-based nanovesicles have the potential to be used as a drug delivery vehicle for wide array of drug molecules. Spanlastics are formed by the self-association of non-ionic surfactants and edge activators in an aqueous phase and have gained attention as promising drug carriers due to their biodegradable, biocompatible, and non-immunogenic structure. In recent years, numerous scientific journals have published research articles exploring the potential of spanlastics to serve as a DDS for various types of drugs as they offer targeted delivery and regulated release of the drugs. Following brief introduction to spanlastics, their structure and methods of preparation, this review focuses on the delivery of various drugs using spanlastics as a carrier via various routes viz. topical, transdermal, ototopical, ocular, oral and nasal. Work carried out by various researchers by employing spanlastics as a carrier for enhancing therapeutic activity of different moieties has been discussed in detail.

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.

Formulation and Evaluation of Hybrid Niosomal In Situ Gel for Intravesical Co-Delivery of Curcumin and Gentamicin Sulfate.

The current study describes the elaboration of a hybrid drug delivery platform for an intravesical application based on curcumin/gentamicin sulfate simultaneously loaded niosomes incorporated into thermosensitive in situ gels. Series of niosomes were elaborated via the thin film hydration method, evaluating the impact of non-ionic surfactants', cholesterol's, and curcumin's concentration. The formulation composed of equimolar ratio of Span 60, Tween 60, and 30 mol% cholesterol was selected as the optimal composition, due to the high entrapment efficiency values obtained for both drugs, and appropriate physicochemical parameters (morphology, size, PDI, and zeta potential), therefore, was further incorporated into Poloxamers (407/188) and Poloxamers and chitosan based in situ gels. The developed hybrid systems were characterized with sol to gel transition in the physiological range, suitable rheological and gelling characteristics. In addition, the formed gel structure at physiological temperatures determines the retarded dissolution of both drugs (vs. niosomal suspension) and sustained release profile. The conducted microbial studies of selected niosomal in situ gels revealed the occurrence of a synergetic effect of the two compounds when simultaneously loaded. The findings indicate that the elaborated thermosensitive niosomal in situ gels can be considered as a feasible platform for intravesical drug delivery.

Invasomes for Enhanced Delivery through the Skin: Evaluation of Systems to Meet with Clinical Challenges.

BACKGROUND: Portage of therapeutic agents directly to the skin (cutaneous/dermal delivery) is the preferable approach in mitigating and curing a variety of skin manifestations, including itching, eczema, acne, psoriasis keratinization, and skin cancer. Dermal delivery reduces side effects associated with systemic therapy and allows maximum utilization of the available doses. Invasomes are the next generation of liposomes with greater flexibility, elasticity, and permeability through the skin than liposomes and ethosomes. OBJECTIVE: This review article highlights various aspects of invasomes, including the structure and composition of invasomes, methods of preparation of invasomes, the mechanism involved in better penetration through the skin, key parameters to be considered for effective permeation, therapeutic applications of invasomes as novel drug delivery systems, and future development and challenges. METHODS: The authors have reviewed various primary and secondary sources, including PUBMED, SCIENCE DIRECT, INFORMA, and patents.com, to collect information on various aspects of invasomes. RESULTS AND CONCLUSION: Invasomes are novel vesicular drug delivery systems that have been used for dermal delivery of drugs for various therapeutic applications. These novel carriers have great ability, and their properties can be highly modulated by varying their composition and concentration of terpenes. Based on all the research reports gathered, it is well proven that these systems have a much higher potential for delivering drugs for skin manifestations and could expand the opportunities for treating various dermatological issues, increasing day by day.

Topical nanocarriers for management of Rheumatoid Arthritis: A review.

Rheumatoid arthritis (RA) is a systemic autoimmune disease manifested by chronic joint inflammation leading to severe disability and premature mortality. With a global prevalence of about 0.3%-1% RA is 3-5 times more prevalent in women than in men. There is no known cure for RA; the ultimate goal for treatment of RA is to provide symptomatic relief. The treatment regimen for RA involves frequent drug administration and high doses of NSAIDs such as indomethacin, diclofenac, ibuprofen, celecoxib, etorcoxib. These potent drugs often have off target effects which drastically decreases patient compliance. Moreover, conventional non-steroidal anti-inflammatory have many formulation challenges like low solubility and permeability, poor bioavailability, degradation by gastrointestinal enzymes, food interactions and toxicity. To overcome these barriers, researchers have turned to topical route of drug administration, which has superior patience compliance and they also bypass the first past effect experienced with conventional oral administration. Furthermore, to enhance the permeation of drug through the layers of the skin and reach the site of inflammation, nanosized carriers have been designed such as liposomes, nanoemulsions, niosomes, ethosomes, solid lipid nanoparticles and transferosomes. These drug delivery systems are non-toxic and have high drug encapsulation efficiency and they also provide sustained release of drug. This review discusses the effect of formulation composition on the physiochemical properties of these nanocarriers in terms of particle size, surface charge, drug entrapment and also drug release profile thus providing a landscape of topically used nanoformulations for symptomatic treatment of RA.

A Comprehensive Review on Nanotechnology-Based Innovations in Topical Drug Delivery for the Treatment of Skin Cancer.

BACKGROUND: Skin is the largest organ of the body and helps to regulate several physiological functions. It acts as a barrier that protects the body against UV-radiation, toxic substances, infections, etc. The abnormal growth of the skin cells is called skin cancer. Different types of skin cancer can be classified as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC); which mainly occur due to chronic exposure to UV- sunlight and pollution. METHODS: The conventional topical treatments of skin cancer such as cream, gel, ointment, etc., are more occlusive and thus they do not penetrate deep into the skin (dermal layer) and remain at the upper part of the skin (epidermal layer). The stratum corneum acts as a physiological barrier for the drug-loaded in the conventional formulation. The novel carrier systems have the potential to facilitate the penetration of the drug deep into the skin (dermal layer) because these have less size and higher flexibility than conventional treatment. CONCLUSION: In the present review, we have discussed various novel carrier systems being investigated for the topical application of chemotherapeutic agents for efficient skin targeting and better dermatological as well as therapeutic benefits with minimal systemic exposure and toxicity.

Insights on the Use of Nanocarriers for Acne Alleviation.

Among the common myths in the cosmetics industry is the perception that acne only happens to teenagers, and specifically to females. However, acne is neither limited to a specific age, nor to a certain gender, it creates a stressful problem for many people. Many chemical treatments for acne were proven to be successful, but when administered as such, they showed many adverse effects, starting from itching to skin dryness and inflammation. Natural remedies have also been explored for acne treatment, and despite their safety, they suffered many stability problems attributed to their physicochemical properties, creating an obstacle for their topical delivery. Therefore, many nanocarriers were used to deliver those chemical and natural remedies topically to maximize their therapeutic potential in acne treatment. The present review discusses the different nanocarriers which were proven successful in improving the acne lesions, focusing on vesicular, lipidic, and polymeric systems.

Biocompatible nanoparticles and vesicular systems in transdermal drug delivery for various skin diseases.

Transdermal drug delivery (TDDS) has been highly explored in the past couple of decades due to benefits such as increased patient compliance, improved drug release, tissue targeting, avoiding the presystemic metabolism in the liver etc. However, the stratum corneum poses as the rate limiting barrier to the permeation of drugs through the skin, which has been a continuous challenge in TDDS. This review covers the various types of nanoparticles and nanoemulsions that are currently being investigated for TDDS applications, desirable physical and chemical characteristics of these systems, their routes of penetration through the skin, and summarizes recent advances using these systems in treating conditions such as alopecia, wound healing, psoriasis, and melanoma. Additionally, synergistic effect of iontophoresis and mechanical force mediated drug delivery will be reviewed.

Recent Advances in Antioxidant Cosmeceutical Topical Delivery.

Antioxidants are among the most important cosmeceuticals, with proven ability of inhibiting cellular damage. The topical skin administration of antioxidants is essential for minimizing skin aging and achieving better skin protection against harmful free radicals. However, their unfavorable physiochemical properties such as chemical instability, excessive hydrophilicity or lipophilicity and others could be a great obstacle against their skin promising effects as well as their delivery to deeper skin layers. These problems could all be remedied through the use of delivery carriers. The present review discusses the various delivery carriers which were proven successful in improving the beneficial effects of antioxidants against skin aging, namely different vesicular systems, lipidic systems, polymeric systems and carbon nanotubes, and their applications in topical antioxidant delivery.

Immunological axis of curcumin-loaded vesicular drug delivery systems.

Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.

Vesicular systems employing natural substances as promising drug candidates for MMP inhibition in glioblastoma: A nanotechnological approach.

Glioblastoma multiforme (GBM), one of the most lethal Brain tumors, characterized by its high invasive nature and increased mortality rates forms a major bottleneck in transport of therapeutics across the Blood Brain Barrier (BBB). Matrix metalloproteinases (MMPs) are classified as enzymes, which are found to be up regulated in the Glioma tumor microenvironment and thus can be considered as a target for inhibition for curbing GBM. Many chemotherapeutics and techniques have been employed for inhibiting MMPs till now but all of them failed miserably and were withdrawn in clinical trials due to their inability in restricting the tumor growth or increasing the overall survival rates. Thus, the quest for finding the suitable MMP inhibitor is still on and there is a critical need for identification of novel compounds which can alter the BBB permeability, restrain tumor growth and prevent tumor recurrence. Currently, naturally derived substances are gaining widespread attention as tumor inhibitors and many studies have been reported by far highlighting their importance in restricting MMP expression thus serving as chemotherapeutics for cancer due to their minimal toxicity. These substances may serve as probable candidates for inhibiting MMP expression in GBM. However, targeting and delivering the inhibitor to its target site is an issue that needs to be overcome in order to attain maximum specificity and sustained release. The birth of nanotechnology served as a boon in delivering drugs to the most complicated areas thus paving way for Nano drug delivery. An efficient Nano carrier with ability to cross the BBB and competently kill the Glioma cells forms the prerequisite for GBM chemotherapy. Vesicular drug delivery systems are one such class of carriers, which have the capacity to release the drug at a predetermined rate at the target site thus minimizing any undesirable side effects. Exploiting vesicular systems as promising Nano drug carriers to formulate naturally derived substances, that can bypass the BBB and act as an inhibitor against MMPs in GBM is the main theme of this review.

Vesicular Systems Containing Curcumin and Their Applications in Respiratory Disorders - A Mini Review.

BACKGROUND: Vesicular systems like nanotechnology and liposomes are gaining tremendous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance. OBJECTIVE: The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin. METHODS: We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases. RESULTS: Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on. CONCLUSION: This mini review, in this direction, tries to highlight the key research interventions employing vesicular systems of drug delivery with curcumin.