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      Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals

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          Abstract

          During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.

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          Most cited references182

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          Nanocarriers as an emerging platform for cancer therapy.

          Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.
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            PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.

            Coating the surface of nanoparticles with polyethylene glycol (PEG), or "PEGylation", is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.
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              Nanoparticles in medicine: therapeutic applications and developments.

              Nanotechnology is the understanding and control of matter generally in the 1-100 nm dimension range. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as ultra small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                06 December 2020
                December 2020
                : 12
                : 12
                : 1184
                Affiliations
                [1 ]Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; alam.zeb@ 123456riphah.edu.pk (A.Z.); bradchoi@ 123456hanyang.ac.kr (H.-I.C.); lch2162@ 123456hanyang.ac.kr (C.-H.L.); tjddnd55@ 123456hanyang.ac.kr (S.-W.B.); qleh0826@ 123456hanyang.ac.kr (C.-W.L.); onbae@ 123456hanyang.ac.kr (O.-N.B.)
                [2 ]Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; isra.rana@ 123456riphah.edu.pk (I.R.); namrah.khan@ 123456riphah.edu.pk (N.K.); tabassamsadia96@ 123456yahoo.com (S.T.A.); sahar.tariq2011@ 123456gmail.com (N.u.S.); aroojalvi@ 123456hotmail.com (A.M.A.); fawad.shah@ 123456riphah.edu.pk (F.A.S.)
                [3 ]Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan; fudin@ 123456qau.edu.pk
                [4 ]Institute of Drug Research and Development, College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
                Author notes
                [* ]Correspondence: eicosa@ 123456cnu.ac.kr (J.-S.P.); jinkikim@ 123456hanyang.ac.kr (J.-K.K.); Tel.: +82-42-821-5932 (J.-S.P.); +82-31-400-5808 (J.-K.K.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-3753-034X
                https://orcid.org/0000-0003-4719-6832
                https://orcid.org/0000-0001-6565-2008
                https://orcid.org/0000-0003-0583-2116
                https://orcid.org/0000-0002-4081-213X
                https://orcid.org/0000-0002-1944-1231
                Article
                pharmaceutics-12-01184
                10.3390/pharmaceutics12121184
                7762162
                33291312
                615b33bf-3029-408f-a0ec-db8cde608956
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 October 2020
                : 02 December 2020
                Categories
                Review

                biopharmaceuticals,recombinant dna technology,delivery and formulation challenges,nanocarriers,proteins,monoclonal antibodies,enzymes,vaccines,cytokines,hormones

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