9 research outputs found
Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics
Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that cause millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients’ disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient’s physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.All the authors are highly grateful and acknowledge to the authority of the respective departments and institutions for their support in carrying out this research. The authors also express their sincere gratitude to the unknown referee for critically reviewing the manuscript and suggesting useful changes.
This research was funded by "Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) del Gobierno de Canarias” (No. ProID2020010134), and o´Caja Canarias (Project No. 2019SP43).Peer reviewe
Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics
The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry’s screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports
Effect of Polyethylene Glycol on Properties and Drug Encapsulation–Release Performance of Biodegradable/Cytocompatible Agarose–Polyethylene Glycol–Polycaprolactone Amphiphilic Co-Network Gels
We synthesized agarose–polycaprolactone
(Agr-PCL) bicomponent and Agr–polyethylene glycol–PCL
(Agr-PEG-PCL) tricomponent amphiphilic co-network (APCN) gels by the
sequential nucleophilic substitution reaction between amine-functionalized
Agr and activated halide terminated PCL or PCL-<i>b</i>-PEG-<i>b</i>-PCL copolymer for the sustained and localized delivery
of hydrophilic and hydrophobic drugs. The biodegradability of the
APCNs was confirmed using lipase and by hydrolytic degradation. These
APCN gels displayed good cytocompatibility and blood compatibility.
Importantly, these APCN gels exhibited remarkably high drug loading
capacity coupled with sustained and triggered release of both hydrophilic
and hydrophobic drugs. PEG in the APCNs lowered the degree of phase
separation and enhanced the mechanical property of the APCN gels.
The drug loading capacity and the release kinetics were also strongly
influenced by the presence of PEG, the nature of release medium, and
the nature of the drug. Particularly, PEG in the APCN gels significantly
enhanced the 5-fluorouracil loading capacity and lowered its release
rate and burst release. Release kinetics of highly water-soluble gemcitabine
hydrochloride and hydrophobic prednisolone acetate depended on the
extent of water swelling of the APCN gels. Cytocompatibility/blood
compatibility and pH and enzyme-triggered degradation together with
sustained release of drugs show great promise for the use of these
APCN gels in localized drug delivery and tissue engineering applications
Self-Assembly of Partially Alkylated Dextran-<i>graft</i>-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties
Key
issues of injectable hydrogels are incapability of loading
hydrophobic drugs due to insolubility of drugs in aqueous prepolymer
solution as well as in hydrogel matrix, and high water swelling, which
leads to poor mechanical and bioadhesive properties. Herein, we report
that self-assembly of partially long-chain alkylated dextran-<i>graft</i>-polyÂ[(2-dimethylamino)Âethyl methacrylate] copolymer
in aqueous solution could encapsulate pyrene, a hydrophobic probe,
griseofulvin, a hydrophobic antifungal drug, and ornidazole, a hydrophilic
antibiotic. Addition of activated chloride terminated polyÂ(ethylene
glycol) (PEG) into the guest molecules loaded copolymer solution produced
an injectable dextran-<i>graft</i>-polyÂ[(2-dimethylamino)Âethyl
methacrylate]-linked-PEG conetwork hydrogel. The alkylated hydrogels
exhibited zero order release kinetics and were mechanically tough
(50–54 kPa storage modulus) and bioadhesive (8–9 kPa).
The roles of alkyl chains and dextran on the drug loading-release
behavior, degradation behavior, gelation time, and the mechanical
property of the hydrogels have been studied in details. Additionally,
DNA hybrid composite hydrogel was formed owing to the cationic nature
of the prepolymer solution and the hydrogel. Controlled alkylation
of a prepolymer thus highlights the potential to induce and enhance
the hydrogel property
Multifunctionalization of Poly(vinylidene fluoride)/Reactive Copolymer Blend Membranes for Broad Spectrum Applications
Simultaneous
immobilization and cross-linking of antifouling/low
toxic polymers, e.g., polyÂ(ethylenimine) (PEI), dextran (Dex), agarose
(Agr), polyÂ(ethylene glycol) (PEG), PEI–Dex, and PEI–PEG
conjugates, and stimuli-responsive copolymers on a porous membrane
surface in mild reaction conditions is desirable for the enhancement
of hydrophilicity, antifouling character, cytocompatibility, and inducing
stimuli-responsive behavior. Grafting to technique is required since
the precursors of most of these macromolecules are not amenable to
surface-initiated polymerization. In this work, we report a versatile
process for the simultaneous immobilization and cross-linking of a
library of macromolecules on and into the blend membrane (PVDF-blend)
of polyÂ(vinylidene fluoride) and polyÂ(methyl methacrylate)-<i>co</i>-polyÂ(chloromethylÂstyrene). Sequential nucleophilic
substitution reaction between activated halide moieties of the copolymer
and amine groups of different macromolecules readily provided series
of modified membranes. These membranes exhibited antifouling property
superior to that of the unmodified membrane. The effectiveness of
this technique has been demonstrated by the immobilization of pH or
both pH- and temperature-responsive copolymer on PVDF-blend membrane
for responsive separation of polyÂ(ethylene oxide) and bovine serum
albumin. Silver nanoparticles were also anchored on the select modified
membranes surfaces for the enhancement of antibiofouling property.
Our approach is useful to obtain verities of functional membranes
and selection of membrane for a particular application