Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid–polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core–shell nanoparticles, hollow core–shell nanoparticles, biomimetic lipid–polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core–shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core–shell-structured LPHNPs.

Drug delivery via the oral route has always been challenging for poorly soluble drugs. Acid-induced hydrolysis, enzymatic degradation, and poor mucosal absorbency remain the primary hiccups for effective oral delivery of medications. With the advent of nanotechnology, nanostructured lipid carriers (NLCs) have emerged as a promising delivery carrier that can circumvent gastrointestinal tract (GIT) barriers hindering the solubility and bioavailability of such drugs. These NLCs can efficiently transport drug moieties across intestinal membranes shielding medications from intestinal pH and enzymatic degradation. Because they are composed of lipidic materials, they can be easily absorbed or taken up by various pathways such as transcellular absorption, paracellular transport, and M-cell uptake. Such mechanisms not only improve the absorption and solubility of drugs but also augment bioavailability and residence time and may bypass first-pass metabolism. This review explores the diverse applications of nanostructured lipid carriers (NLCs) in oral drug delivery for various medical conditions, shedding light on their current regulatory status, including FDA-approved options and those in pre/clinical stages. The review also features patented NLC formulations. It provides valuable insights into how NLCs can be harnessed for effective oral drug delivery and outlines recent advancements in optimizing their performance to tackle gastrointestinal barriers, thus opening new possibilities for NLCs in future pharmaceutical applications.

Significance: Genome fluidity is directly associated with the emergence and evolution of many bacterial pathogens. Horizontally acquired genetic elements, which harbor fitness traits, are open source for the bacterial evolution. The genome of Vibrio cholerae is equipped with multiple mobile genetic elements (MGEs), which are crucial for disease development and survival. The present study engineered the genome of a well characterized clinical V. cholerae strain N16961 and reported ( i ) stability of MGEs in cholera pathogen, ( ii ) interactions between the core genome and MGEs, and ( iii ) role of MGEs in the modulation of cellular proteome. The engineered strain could be a potential candidate for understanding evolution of cholera pathogen and development of new therapeutic interventions.

Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested ∼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs.

In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer–drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light.