Vascular targeted nanotherapeutic approach for obesity treatment

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obesity 104 endocrinologydiseases
orlistat 3 endocrinologydiseasesdrugs
rosiglitazone 1 endocrinologydiseasesdrugs

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orlistat 2961 drugs.[8]–[10] Due to adverse effects, many anti-obesity drugs have been removed from the market, leaving only orlistat for long-term treatment of obesity.[10]–[15] Moreover, the pharmaceutical drugs are useful for a limited
orlistat 11029 drugs were approved by U.S. Food and Drug Administration (FDA) for long-term treatment of obesity: orlistat and sibutramine. Due to negative cardiovascular effects that resulted in the death of patients, sibutramine
orlistat 11345 weight in obese subjects since its approval by FDA in 1997. Unfortunately, after its termination only orlistat remains for a long-term management of obesity.[10],[15]Bariatric surgery is recommended for morbidly
rosiglitazone 37817 descriptionBiodegradable polymeric NPs were made from a poly(lactide-coglycolide)-b-PEG copolymer. Therapeutic compounds, rosiglitazone (Rosi), and 16,16-dimethyl prostaglandin E2 (PGE2) analogs were encapsulated within the NPs. Vascular
Select Disease Character Offset Disease Term Instance
obesity 91 Title: International Journal of NanomedicineVascular targeted nanotherapeutic approach for obesity treatmentNicole Remaliah Samantha SibuyiMervin MeyerMartin Opiyo OnaniAmanda SkepuAbram Madimabe Madiehe1Department
obesity 1007 diabetes, cancer, and cardiovascular diseases. Pharmacotherapy remains the mainstay for the management of obesity ; however, its usefulness is limited due to poor drug efficacy, non-specificity and toxic side effects.
obesity 1179 non-specificity and toxic side effects. Therefore, novel approaches that could provide insights into obesity and obesity-associated diseases as well as development of novel anti-obesity treatment modalities or
obesity 1191 non-specificity and toxic side effects. Therefore, novel approaches that could provide insights into obesity and obesity -associated diseases as well as development of novel anti-obesity treatment modalities or improvement
obesity 1256 provide insights into obesity and obesity-associated diseases as well as development of novel anti- obesity treatment modalities or improvement on the existing drugs are necessary. While the ideal treatment of
obesity 1366 treatment modalities or improvement on the existing drugs are necessary. While the ideal treatment of obesity should involve early intervention in susceptible individuals, targeted nanotherapy potentially provides
obesity 1790 primates, thus providing a proof of concept that targeted nanotherapy can be a feasible treatment for obesity . This review presents a brief global survey of obesity, its impact on human health, its current treatment
obesity 1845 nanotherapy can be a feasible treatment for obesity. This review presents a brief global survey of obesity , its impact on human health, its current treatment and their limitations, and the role of angiogenesis
obesity 1986 current treatment and their limitations, and the role of angiogenesis and PHB in the development of obesity . Finally, the role and potential use of nanotechnology coupled with targeted drug delivery in the treatment
obesity 2105 the role and potential use of nanotechnology coupled with targeted drug delivery in the treatment of obesity are discussed.IntroductionObesity has reached epidemic proportions worldwide[1] and contributes to the
obesity 2414 (T2D),[2] cardiovascular diseases (CVDs),[3] cancer,[4] and hypertension.[5] The current treatment of obesity involves lifestyle modification, pharmacotherapy, and surgery. Pharmacotherapy is the cornerstone of
obesity 2523 involves lifestyle modification, pharmacotherapy, and surgery. Pharmacotherapy is the cornerstone of obesity treatment and can be used alone or in combination with diet and surgery.[6],[7] However, the drugs used
obesity 2657 alone or in combination with diet and surgery.[6],[7] However, the drugs used for the management of obesity are tainted by the adverse health risks associated with drug treatment due to their off-target side
obesity 2899 which reduces the sensitivity and efficacy of the drugs.[8]–[10] Due to adverse effects, many anti- obesity drugs have been removed from the market, leaving only orlistat for long-term treatment of obesity.[10]–[15]
obesity 2997 anti-obesity drugs have been removed from the market, leaving only orlistat for long-term treatment of obesity .[10]–[15] Moreover, the pharmaceutical drugs are useful for a limited period (≤2 years) to avoid
obesity 3303 of treatment is often followed by disease relapse.[11]Alternative or novel strategies that can treat obesity and sustain the weight loss are required. Such treatments are of utmost importance in health economics
obesity 3629 reason, vascular targeted therapy is receiving a considerable amount of attention as a potential anti- obesity therapy. The ability to ferry therapeutic materials directly to pathological cells with no effect on
obesity 3902 conventional pharmacotherapy.[16] Strategies that target prohibitin (PHB) as a vascular marker for obesity have been explored using a PHB targeting ligand (adipose-homing peptide, AHP) to develop targeted therapy[16]
obesity 4472 unique properties of the nanosystems.[17],[18] The feasibility of the vascular targeted nanotherapy in obesity is reviewed in this paper.Obesity: a global epidemicObesity is a metabolic and genetic disorder that
obesity 4734 whereby energy intake exceeds energy expenditure for a prolonged period.[21] If not properly managed, obesity leads to the development of chronic diseases such as T2D,[2] CVDs,[3] various forms of cancer,[4] and
obesity 5045 medical care costs, decreased quality of life, and reduced life expectancy.[6],[7]The prevalence of obesity has increased dramatically worldwide and has become a fast growing epidemic in both developed and developing
obesity 5193 has become a fast growing epidemic in both developed and developing countries.[22] The increase in obesity rates can be attributed to gene-by-environment interactions, urbanization, lack of physical activity,
obesity 6038 have the least obese and overweight population. Similar trends in the prevalence of overweight and obesity in South African adults have been reported, indicating that South Africa (SA) is not immune to this
obesity 6271 strategies to combat these rates, WHO predicts that by 2025, 60% of deaths worldwide will be caused by obesity -associated chronic diseases (CVDs, T2D, stroke, and cancers).[24],[25] In SA, chronic diseases currently
obesity 6496 43% mortality rate.[26] These projections highlight the urgent need and significance to address the obesity epidemic.[23],[24]Pathophysiology of obesityPhysiologically, the white adipose tissues (WATs) play a
obesity 6541 highlight the urgent need and significance to address the obesity epidemic.[23],[24]Pathophysiology of obesity Physiologically, the white adipose tissues (WATs) play a crucial role in the development of obesity and
obesity 6640 obesityPhysiologically, the white adipose tissues (WATs) play a crucial role in the development of obesity and could serve as the best target for obesity interventions.[27] A better understanding of the development
obesity 6687 tissues (WATs) play a crucial role in the development of obesity and could serve as the best target for obesity interventions.[27] A better understanding of the development and physiological roles of WAT is important,
obesity 6874 roles of WAT is important, because this will help to unveil possible new therapeutic approaches for obesity , as well as the prevention of progression to obesity-related diseases.Adipose tissue (AT) as an endocrine
obesity 6927 unveil possible new therapeutic approaches for obesity, as well as the prevention of progression to obesity -related diseases.Adipose tissue (AT) as an endocrine organThere are two types of AT in mammals, namely
obesity 7216 whereas the BAT serves as an energy dissipating organ as shown in Figure 2. The WATs are responsible for obesity and obesity-induced disorders;[28] hence, the focus of this study is mainly on the WAT and its effect
obesity 7228 serves as an energy dissipating organ as shown in Figure 2. The WATs are responsible for obesity and obesity -induced disorders;[28] hence, the focus of this study is mainly on the WAT and its effect on the development
obesity 7348 disorders;[28] hence, the focus of this study is mainly on the WAT and its effect on the development of obesity and obesity-induced diseases. WAT is a loose connective tissue comprised of various cell types held
obesity 7360 hence, the focus of this study is mainly on the WAT and its effect on the development of obesity and obesity -induced diseases. WAT is a loose connective tissue comprised of various cell types held together by
obesity 8082 visceral depot, but the two function in a coordinated and compensatory manner in the development of obesity and obesity-related diseases.[28]Physiological functions of WATs include the provision of insulation
obesity 8094 depot, but the two function in a coordinated and compensatory manner in the development of obesity and obesity -related diseases.[28]Physiological functions of WATs include the provision of insulation to internal
obesity 9460 adipocytes) and hyperplasia (increase in number of adipocytes) in the WAT during the development of obesity results in dysregulated secretion of adipokines and malfunctioning of the WAT.[32]–[37] As such, WAT
obesity 9701 the vascular system can serve as an attractive target for intervention and effective treatment for obesity and its associated disorders.[27],[33]–[37],[43]Conventional treatment of obesityObesity is a chronic
obesity 9785 effective treatment for obesity and its associated disorders.[27],[33]–[37],[43]Conventional treatment of obesity Obesity is a chronic disease, and there is currently no treatment that can sustain weight loss for a
obesity 10378 T2D.[39],[40]Pharmacotherapy is an option for patients with body mass index (BMI) ≥27 kg/m2, with at least one obesity -related chronic disease risk factor.[10] The treatment is recommended for patients who had gone through
obesity 10709 is now also prescribed to obese children and adolescents at a greater health risk.[6],[41] The anti- obesity drugs are reliable for the period of use, ≤6 months for short term and ≤2 years for long term.[10]
obesity 11020 only two drugs were approved by U.S. Food and Drug Administration (FDA) for long-term treatment of obesity : orlistat and sibutramine. Due to negative cardiovascular effects that resulted in the death of patients,
obesity 11392 FDA in 1997. Unfortunately, after its termination only orlistat remains for a long-term management of obesity .[10],[15]Bariatric surgery is recommended for morbidly obese patients (BMI ≥40 kg/m2) or patients
obesity 11588 or patients with BMI of 30–40 kg/m2 and at least one life-threatening health risk associated with obesity . It involves modifying the gastrointestinal tract to reduce caloric intake or nutrient absorption by
obesity 11764 intake or nutrient absorption by the body, thereby reducing body weight.[42],[43] Attempts to treat obesity by reducing food intake, with or without anti-obesity drugs are well-known, as are their limitations,
obesity 11818 reducing body weight.[42],[43] Attempts to treat obesity by reducing food intake, with or without anti- obesity drugs are well-known, as are their limitations, difficulties, and general lack of success in maintaining
obesity 12211 need and urgency to find novel or alternative approaches that could be used to treat and/or prevent obesity at an early stage and improve human health and quality of life. Among the most important goals of obesity
obesity 12317 obesity at an early stage and improve human health and quality of life. Among the most important goals of obesity treatment are: 1) a preferential reduction of abdominal fat/WAT, 2) an amelioration of obesity-related
obesity 12412 goals of obesity treatment are: 1) a preferential reduction of abdominal fat/WAT, 2) an amelioration of obesity -related health risks, 3) an improvement in comorbidities and quality of life, and 4) a reduction in
obesity 12585 quality of life, and 4) a reduction in mortality rate.[6],[47] Approaches targeted at the root cause of obesity (ie, the pathological WAT) have been shown to be successful in reducing body weight with minimal adverse
obesity 15744 system for growth, proliferation, and survival. Diabetic retinopathy, rheumatoid arthritis, cancer, obesity , and autoimmune disease are some of the diseases in which angiogenesis is switched on.[16] These diseases
obesity 16085 vasculature of the diseased cells provide a better approach with sustainable health benefits.Angiogenesis in obesity Angiogenesis is an important factor in the expansion of WATs.[65]–[67] AT growth and expansion through
obesity 16399 tissue. Hypertrophic and hyperplastic growth of adipocytes are excessive during the development of obesity . This requires an expansion of blood vessels (angiogenesis) to allow nutrients and oxygen to reach the
obesity 16565 (angiogenesis) to allow nutrients and oxygen to reach the newly formed and expanding adipocytes.[66]Like cancer, obesity is associated with vascular disorders,[53]–[55] and since obesity progression is highly dependent
obesity 16633 expanding adipocytes.[66]Like cancer, obesity is associated with vascular disorders,[53]–[55] and since obesity progression is highly dependent on angiogenesis, it could be reversed by using treatment strategies
obesity 16775 angiogenesis, it could be reversed by using treatment strategies that inhibit this process.[50] In obesity , the WATs are highly vascularized in order to support the expanding tissues.[66] As a result, the WATs
obesity 17163 which is accompanied by the overexpression of certain cell surface receptors during the development of obesity . The receptors could be useful as targets for a therapeutic intervention.[49],[66] Thus, inhibition
obesity 17374 angiogenesis in the obese WAT vasculature serves as a plausible therapeutic option for treatment of obesity .[65],[66]Angiogenesis in WATs, like in cancer, is dependent on the balance between proangiogenic and
obesity 18037 angiogenesis by targeting of proangiogenic factors was shown to regulate WAT mass in animal models of obesity and in vitro.[33],[67],[68]The widely studied angiogenesis inhibitors TNP 470, angiostatin, and endostatin[69]
obesity 19248 conjugated to apoptotic agents, thus preventing WAT growth in genetic and diet-induced animal models of obesity .[67],[71] PHB was also explored as an anti-angiogenic target in obesity. Kolonin et al[16] discovered
obesity 19320 diet-induced animal models of obesity.[67],[71] PHB was also explored as an anti-angiogenic target in obesity . Kolonin et al[16] discovered that PHB is overexpressed in the WAT vasculature of obese mice and further
obesity 19584 D(KLAKLAK)2 or KLA can be delivered into the WAT vasculature of diet-induced obese mice and reverse obesity . The KLA peptide is only toxic to mammalian cells when it is internalized, and once inside the cells,
obesity 20066 purpose, angiogenesis proved to be an attractive target for therapeutic intervention for reversal of obesity . Several studies demonstrated the efficiency of anti-angiogenic therapy in animal models of obesity
obesity 20166 obesity. Several studies demonstrated the efficiency of anti-angiogenic therapy in animal models of obesity as discussed in the following section.[16],[66]PHB and its role in obesityThe role and function of PHB
obesity 20241 therapy in animal models of obesity as discussed in the following section.[16],[66]PHB and its role in obesity The role and function of PHB in cancer and obesity has been extensively reviewed.[72]–[75] PHB is a
obesity 20291 the following section.[16],[66]PHB and its role in obesityThe role and function of PHB in cancer and obesity has been extensively reviewed.[72]–[75] PHB is a 30-kDa multifunctional protein that plays a crucial
obesity 21564 the diseases in which PHB is implicated are shown in Table 1. PHB was reported to be overexpressed in obesity ,[16] cancer, and diabetes and could serve as a potential biomarker for therapeutic intervention.[74],[78],[79]
obesity 23277 inhibited proliferation of Caco-2 colon cancer cells.[83]PHB is also involved in the development of obesity and WAT remodeling.[16] Since this discovery, PHB was used as a vascular marker for obesity. Independent
obesity 23369 development of obesity and WAT remodeling.[16] Since this discovery, PHB was used as a vascular marker for obesity . Independent studies confirmed that molecules attached to AHP with amino acid sequence CKGGRAKDC are
obesity 23963 diseases.[16],[77],[78],[87] Targeted nanotherapy is currently being explored as a potential treatment for obesity in a rodent and non-human primate models of diet-induced obesity, by targeting the vascular system that
obesity 24028 explored as a potential treatment for obesity in a rodent and non-human primate models of diet-induced obesity , by targeting the vascular system that supports the growth of hypertrophic adipocytes.[17],[18],[78],[85]Disease-associated
obesity 29546 revolutionize medicine,[94],[106],[107] it can provide an essential breakthrough in the fight against obesity and metabolic diseases through targeted drug delivery.[94]Potential application of nanotechnology in
obesity 29655 and metabolic diseases through targeted drug delivery.[94]Potential application of nanotechnology in obesity Preclinical studies have covered the basis and paved avenues for vascular targeted nanotherapy as a treatment
obesity 29783 have covered the basis and paved avenues for vascular targeted nanotherapy as a treatment option for obesity in animal models.[18],[84],[108]Figure 3 summarizes the initial steps toward developing a successful
obesity 29995 vascular targeted nanotherapy, in order to assess the feasibility of the strategy for the treatment of obesity as demonstrated by independent studies.[16]–[18],[84],[85] Targeted nanotherapy can be developed by
obesity 30536 cancer therapy.[99],[109]–[111]Nanotherapy targeted at ECs in the WAT vasculature for reversal of obesity in preclinical studies has been documented; most of the studies targeted PHB as the WAT vascular marker.[17],[18],[84],[85]
obesity 30994 led to fat resorption and reduced WAT mass with the consequent reduction of the total body weight and obesity reversal.[16] Incorporating nanotechnology into the same strategy enhanced the efficacy of the treatment,
obesity 31222 threefold higher than the AHP-KLA bi-conjugate.[18]The beneficial effect of PHB-targeted nanotherapy in obesity treatment is summarized in Table 2. The researchers demonstrated that when AHP (PHB-targeting ligand)
obesity 31850 oncomirs (miR-361)[77] and FLs (FL3 and 37)[80],[81] which showed more or less the same effects as AHP.In obesity , the widely used ligand is AHP which demonstrated high specificity for PHB. Specificity of AHP for PHB
obesity 33625 liposomes,[1],[17] and polymeric NPs.[108] As such, PHB-targeted nanotherapy could be the key to combat obesity and obesity-associated diseases (cancer, CVDs, and diabetes). PHB proved to be a key factor that links
obesity 33637 liposomes,[1],[17] and polymeric NPs.[108] As such, PHB-targeted nanotherapy could be the key to combat obesity and obesity -associated diseases (cancer, CVDs, and diabetes). PHB proved to be a key factor that links these diseases,[76]
obesity 34013 Table 2 highlight the potential and feasibility of vascular-targeted nanotherapy for the treatment of obesity . The case studies for PHB-targeted nanotherapy in obesity are discussed below:Case study 1: KLA-encapsulated
obesity 34071 vascular-targeted nanotherapy for the treatment of obesity. The case studies for PHB-targeted nanotherapy in obesity are discussed below:Case study 1: KLA-encapsulated liposomes for PHB targeted deliveryNP descriptionLiposomes
obesity 35880 with AHP-KLA for the same duration.[18]Box 1Beneficial effects of vascular targeted nanotherapy in obesity • Increases the specificity of drugs by targeting disease-associated markers• Ability to passively
obesity 39811 PGE2-loaded NPs reduced serum levels of Chol, TAGs, and insulin.[108] Therefore, this indicated that obesity can be reduced by coupling vasculature-targeted nanomedicine and AT transformation.Interestingly, BAT
obesity 40127 rest. Thus, activation of BAT or transformation of WAT to BAT presents another therapeutic target for obesity . Through cold exposure or stimulation of the sympathetic nervous system, white adipocytes can be converted
obesity 41093 vascular targeted strategies in conjunction with nanotechnology have potential for the treatment of obesity and its comorbidities.[17],[18],[77],[85],[108] This vascular-targeted strategy has more benefits when
obesity 41545 Candidate drugs for this strategy are not limited to the ones mentioned in this review, but other anti- obesity drugs (current or withdrawn) can also be loaded into the nanocarriers for disease treatment. In fact,
obesity 41766 molecules can be incorporated into one NP due to their larger surface area. Withdrawn drugs with anti- obesity effects could be revived by this novel, attractive, and plausible strategy for the treatment of obesity.[6],[17],[18],[108]
obesity 41870 anti-obesity effects could be revived by this novel, attractive, and plausible strategy for the treatment of obesity .[6],[17],[18],[108] Strategies that manipulate angiogenesis, such as anti-angiogenic inhibitors and
obesity 42747 three case studies discussed in the review also demonstrate the strategy’s potential for treatment of obesity [17],[18],[98] and could potentially pave the way toward improving the treatment of obesity and its related
obesity 42838 treatment of obesity[17],[18],[98] and could potentially pave the way toward improving the treatment of obesity and its related metabolic diseases.ConclusionThe current anti-obesity drugs are limited by short circulation
obesity 42908 toward improving the treatment of obesity and its related metabolic diseases.ConclusionThe current anti- obesity drugs are limited by short circulation time, insolubility, and non-selectivity of the drugs, which in
obesity 43196 the bystander toxicity effects to healthy tissues that have led to the discontinuation of many anti- obesity drugs.[6],[10],[12]–[15] This review shows that targeted therapeutic strategies can be used to overcome
obesity 43754 toward non-diseased cells. Vascular targeting showed promising results in the reversal of diet-induced obesity in mice[16] and non-human primates.[86] Therefore, targeted nanotherapy offers a great opportunity for
obesity 43882 non-human primates.[86] Therefore, targeted nanotherapy offers a great opportunity for the treatment of obesity through increased selectivity and sensitivity of the treatment. The concept of targeted drug delivery
obesity 44086 delivery coupled with nanotechnology is thus an attractive and plausible strategy for the treatment of obesity .[17],[18],[83],[85]Figure 1The global prevalence of overweight (A) and obesity (B) in both male and
obesity 44165 for the treatment of obesity.[17],[18],[83],[85]Figure 1The global prevalence of overweight (A) and obesity (B) in both male and female adults.Notes: The data represent 1975 to 2016 statistics for adults aged
obesity 44760 from: (B) World Health Organization (WHO). Global Health Observatory data repository. Prevalence of obesity among adults, BMI ≥ 30, age-standardized. Estimates by WHO region. Available from: http://apps.who.int/gho/data/view.main.REGION2480A?lang=en.
obesity 45085 2017. All Rights Reserved.[26]Figure 2Adipose tissue structure and function and the pathophysiology of obesity .Notes: During positive energy balance, increase in adipocyte number or size in the WAT leads to the
obesity 45208 positive energy balance, increase in adipocyte number or size in the WAT leads to the development of obesity and WAT dysfunction. Adipocyte size is reduced during energy restriction or starvation, which leads
obesity 45425 normalization of WAT function. ↑ and ↓ arrows indicate the increase and decrease of adipokines during obesity development.Abbreviations: +ve, positive; AT, adipose tissue; bal, balance; bat, brown adipose tissue;
obesity 45669 white adipose tissue.Figure 3Initial steps in the development and assessment of targeted nanotherapy in obesity .Notes: Preclinical phase in nanotherapy development involves synthesis, functionalization, and characterization
obesity 48506 nanoparticles; FLs, flavaglines; WAT, white adipose tissue.Table 2PHB-targeted NP for the treatment of obesity NP typeComposition and size of NPs (nm)Disease modelDosageAction of NPsReferenceLiposomesPC and Chol,

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