Hyaluronic acid-engineered Bcl-2 inhibitor nanocrystals for site-specific delivery to breast tumor cells.

Aim: This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. Materials & methods: An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of in vitro drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. Results: HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive in vitro cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (IC50: 2.00 µg/ml) compared with VEN-NCs. Conclusion: Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs.

Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient's perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product's stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development.

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed.

Chondroitin Sulfate: Emerging biomaterial for biopharmaceutical purpose and tissue engineering.

Chondroitin Sulfate (CS) is an anionic hetero polysaccharide possessing anti-inflammatory, antioxidant, antitumor, anticoagulant and antithrombogenic activities. It is biodegradable and biocompatible in nature. Further, it inherits the ability of active and subcellular targeting due to its affinity for CD 44 receptors and glycosylation enzymes, which are overexpressed on the surface of tumor cells and intracellular organelles respectively. CS is known to degrade in presence of physiological stimuli, the hyaluronidase (HAase) enzyme and reactive oxygen species (ROS), assisting in site specific drug release. Due to these properties, it serve as a promising biomaterial for drug delivery and tissue engineering. In this review, the fundamental theory of CS, CS-based nanocarriers for the delivery of biopharmaceuticals and stimuli sensitive delivery systems such as HAase and ROS responsive nanocarriers for tumor targeted delivery are discussed critically. In addition, the manuscript describes the application of CS-based tissue constructs in tissue engineering and wound healing.

Panorama of dissolving microneedles for transdermal drug delivery.

Recently, microfabrication technology has been developed to increase the permeability of drugs for transdermal delivery. Microneedles are ultra-small needles usually in the micron size range (different dimensions in micron), generate pores, and allow for delivery of local medication in the systemic circulation via skin. The microneedles have been available in dissolving, solid, coated, hollow, and hydrogel-based microneedles. Dissolving microneedles have been fabricated using micro-molding, photo-polymerization, drawing lithography and droplet blowing techniques. Dissolving microneedles could be a valuable option for the delivery of low molecular weight drugs, peptides, enzymes, vaccines and bio-therapeutics. It consists of water-soluble materials including maltose, polyvinyl pyrrolidone, chondroitin sulfate, dextran, hyaluronic acid, and albumin. The microneedles have almost dissolved after patch removal, leaving only blunt stubs behind, which are easily removable. In this review, we summarize the major building blocks, classification, fabrication techniques, characterization, diffusion models and application of microneedles in diverse area. We also reviewed the regulatory aspects, computational studies, patents, clinical data, and market trends of microneedles.

COVID-19: Pathophysiology, treatment options, nanotechnology approaches, and research agenda to combating the SARS-CoV2 pandemic.

The recent corona virus disease (COVID-19) outbreak has claimed the lives of many around the world and highlighted an urgent need for experimental strategies to prevent, treat and eradicate the virus. COVID-19, an infectious disease caused by a novel corona virus and no approved specific treatment is available yet. A vast number of promising antiviral treatments involving nanotechnology are currently under investigation to aid in the development of COVID-19 drug delivery. The prospective treatment options integrating the ever-expanding field of nanotechnology have been compiled, with the objective to show that these can be potentially developed for COVID-19 treatment. This review summarized the current state of knowledge, research priorities regarding the pandemic and post COVID-19. We also focus on the possible nanotechnology approaches that have proven to be successful against other viruses and the research agenda to combat COVID-19.

Evolution of Nanotechnology in Delivering Drugs to Eyes, Skin and Wounds via Topical Route.

The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated with complications like intravitreal hemorrhage, retinal detachment, endophthalmitis, and cataracts. The skin has a complex structure that serves as numerous physiological barriers to the entry of exogenous substances. Drug localization is an important aspect of some dermal diseases and requires directed delivery of the active substance to the diseased cells, which is challenging with current approaches. Existing therapies used for wound healing are costly, and they involve long-lasting treatments with 70% chance of recurrence of ulcers. Nanotechnology is a novel and highly potential technology for designing formulations that would improve the efficiency of delivering drugs via the topical route. This review involves a discussion about how nanotechnology-driven drug delivery systems have evolved, and their potential in overcoming the natural barriers for delivering drugs to eyes, skin and wounds.

Polymer-drug conjugates: recent advances and future perspectives.

Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such as a combination of polymers and polysaccharides, to explore dual benefits such as combined vehicles and targeting moieties. Polymer heterogeneity, synthesis of PDCs, broad molecular weight distribution, conjugate variability, immunogenicity of polymers, safety, stability, and stringent regulatory approval are the major obstacles to the successful transition of PDCs to the clinic. In this review, we discuss natural and synthetic PDCs combined with computational modeling for diverse pharmaceutical and biomedical applications.